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• W2884353479 abstract "Colorectal cancer (CRC) diagnosis and prognostic stratification are based on histopathologic assessment of cell or nuclear pleomorphism, aberrant mitotic figures, altered glandular architecture, and other phenomic abnormalities. This complexity is driven by oncogenic perturbation of tightly coordinated spatiotemporal signaling to disrupt multiple scales of tissue organization. This review clarifies molecular and cellular mechanisms underlying common CRC histologic features and helps understand how the CRC genome controls core aspects of tumor aggressiveness. It further explores a spatiotemporal framework for CRC phenomics based on regulation of living cells in fundamental and organotypic model systems. The review also discusses tissue homeostasis, considers distinct classes of oncogenic perturbations, and evolution of cellular or multicellular cancer phenotypes. It further explores the molecular controls of cribriform, micropapillary, and high-grade CRC morphology in organotypic culture models and assesses relevant translational studies. In addition, the review delves into complexities of morphologic plasticity whereby a single molecular signature generates heterogeneous cancer phenotypes, and, conversely, morphologically homogeneous tumors show substantive molecular diversity. Principles outlined may aid mechanistic interpretation of omics data in a setting of cancer pathology, provide insight into CRC consensus molecular subtypes, and better define principles for CRC prognostic stratification. Colorectal cancer (CRC) diagnosis and prognostic stratification are based on histopathologic assessment of cell or nuclear pleomorphism, aberrant mitotic figures, altered glandular architecture, and other phenomic abnormalities. This complexity is driven by oncogenic perturbation of tightly coordinated spatiotemporal signaling to disrupt multiple scales of tissue organization. This review clarifies molecular and cellular mechanisms underlying common CRC histologic features and helps understand how the CRC genome controls core aspects of tumor aggressiveness. It further explores a spatiotemporal framework for CRC phenomics based on regulation of living cells in fundamental and organotypic model systems. The review also discusses tissue homeostasis, considers distinct classes of oncogenic perturbations, and evolution of cellular or multicellular cancer phenotypes. It further explores the molecular controls of cribriform, micropapillary, and high-grade CRC morphology in organotypic culture models and assesses relevant translational studies. In addition, the review delves into complexities of morphologic plasticity whereby a single molecular signature generates heterogeneous cancer phenotypes, and, conversely, morphologically homogeneous tumors show substantive molecular diversity. Principles outlined may aid mechanistic interpretation of omics data in a setting of cancer pathology, provide insight into CRC consensus molecular subtypes, and better define principles for CRC prognostic stratification. Understanding oncogenic processes that shape cancer histology is a longstanding objective in pathology.1Heng Y.J. Lester S.C. Tse G.M. Factor R.E. Allison K.H. Collins L.C. Chen Y.Y. Jensen K.C. Johnson N.B. Jeong J.C. Punjabi R. Shin S.J. Singh K. Krings G. Eberhard D.A. Tan P.H. Korski K. Waldman F.M. Gutman D.A. Sanders M. Reis-Filho J.S. Flanagan S.R. Gendoo D.M. Chen G.M. Haibe-Kains B. Ciriello G. Hoadley K.A. Perou C.M. Beck A.H. The molecular basis of breast cancer pathological phenotypes.J Pathol. 2017; 241: 375-391Crossref PubMed Scopus (75) Google Scholar Seminal studies have identified molecular signatures of cancer initiation or progression2Ciriello G. Miller M.L. Aksoy B.A. Senbabaoglu Y. Schultz N. Sander C. Emerging landscape of oncogenic signatures across human cancers.Nat Genet. 2013; 45: 1127-1133Crossref PubMed Scopus (906) Google Scholar and have shown associations with multiple histologic features in tissue sections.1Heng Y.J. Lester S.C. Tse G.M. Factor R.E. Allison K.H. Collins L.C. Chen Y.Y. Jensen K.C. Johnson N.B. Jeong J.C. Punjabi R. Shin S.J. Singh K. Krings G. Eberhard D.A. Tan P.H. Korski K. Waldman F.M. Gutman D.A. Sanders M. Reis-Filho J.S. Flanagan S.R. Gendoo D.M. Chen G.M. Haibe-Kains B. Ciriello G. Hoadley K.A. Perou C.M. Beck A.H. The molecular basis of breast cancer pathological phenotypes.J Pathol. 2017; 241: 375-391Crossref PubMed Scopus (75) Google Scholar However, the utility of genomic data sets in cancer pathology is limited by incomplete understanding of the spatiotemporal dimension of the cancer genome.3Kholodenko B.N. Hancock J.F. Kolch W. Signalling ballet in space and time.Nat Rev Mol Cell Biol. 2010; 11: 414-426Crossref PubMed Scopus (472) Google Scholar How oncogenic processes shape cancer morphology by disruption of signaling pathways that are tightly coordinated in time and space remains poorly understood.3Kholodenko B.N. Hancock J.F. Kolch W. Signalling ballet in space and time.Nat Rev Mol Cell Biol. 2010; 11: 414-426Crossref PubMed Scopus (472) Google Scholar In this review, the complexity of the colorectal cancer (CRC) phenome, that is, the histologic traits driven by oncogenic perturbation of colorectal homeostasis, has been addressed. The genotype–phenotype relationships in biological model systems that have the spatiotemporal resolution to uncover molecular regulation of shape, movements, and three-dimensional (3D) rearrangements of growing cancer cells have been explored. Because the CRC genome is strongly influenced by the preexisting molecular profile of the epithelial cell of origin,4Hoadley K.A. Yau C. Hinoue T. Wolf D.M. Lazar A.J. Drill E. Shen R. Taylor A.M. Cherniack A.D. Thorsson V. Akbani R. Bowlby R. Wong C.K. Wiznerowicz M. Sanchez-Vega F. Robertson A.G. Schneider B.G. Lawrence M.S. Noushmehr H. Malta T.M. Stuart J.M. Benz C.C. Laird P.W. Cancer Genome Atlas NetworkCell-of-origin patterns dominate the molecular classification of 10,000 tumors from 33 types of cancer.Cell. 2018; 173: 291-304.e6Abstract Full Text Full Text PDF PubMed Scopus (1054) Google Scholar controls of epithelial homeostasis have been reviewed.5Lechler T. Fuchs E. Asymmetric cell divisions promote stratification and differentiation of mammalian skin.Nature. 2005; 437: 275-280Crossref PubMed Scopus (763) Google Scholar, 6Jaffe A.B. Kaji N. Durgan J. Hall A. Cdc42 controls spindle orientation to position the apical surface during epithelial morphogenesis.J Cell Biol. 2008; 183: 625-633Crossref PubMed Scopus (268) Google Scholar, 7Bryant D.M. Mostov K.E. From cells to organs: building polarized tissue.Nat Rev Mol Cell Biol. 2008; 9: 887-901Crossref PubMed Scopus (585) Google Scholar Against this background, we consider oncogenic perturbations,8Magudia K. Lahoz A. Hall A. K-Ras and B-Raf oncogenes inhibit colon epithelial polarity establishment through up-regulation of c-myc.J Cell Biol. 2012; 198: 185-194Crossref PubMed Scopus (42) Google Scholar, 9Bryant D.M. Roignot J. Datta A. Overeem A.W. Kim M. Yu W. Peng X. Eastburn D.J. Ewald A.J. Werb Z. Mostov K.E. A molecular switch for the orientation of epithelial cell polarization.Dev Cell. 2014; 31: 171-187Abstract Full Text Full Text PDF PubMed Scopus (132) Google Scholar, 10Deevi R. McClements J. McCloskey K.D. Fatehullah A. Tkocz D. Javadi A. Higginson R. Marsh Durban V. Jansen M. Clarke A. Loughrey M.B. Campbell F.C. Vitamin D3 suppresses morphological evolution of the cribriform cancerous phenotype.Oncotarget. 2016; 7: 49042-49064Crossref PubMed Scopus (7) Google Scholar, 11Deevi R.K. Javadi A. McClements J. Vohhodina J. Savage K. Loughrey M.B. Evergren E. Campbell F.C. Protein kinase C zeta suppresses low- or high-grade colorectal cancer (CRC) phenotypes by interphase centrosome anchoring.J Pathol. 2018; 244: 445-459Crossref PubMed Scopus (4) Google Scholar evolution of specific CRC morphology phenotypes in culture model systems,9Bryant D.M. Roignot J. Datta A. Overeem A.W. Kim M. Yu W. Peng X. Eastburn D.J. Ewald A.J. Werb Z. Mostov K.E. A molecular switch for the orientation of epithelial cell polarization.Dev Cell. 2014; 31: 171-187Abstract Full Text Full Text PDF PubMed Scopus (132) Google Scholar, 10Deevi R. McClements J. McCloskey K.D. Fatehullah A. Tkocz D. Javadi A. Higginson R. Marsh Durban V. Jansen M. Clarke A. Loughrey M.B. Campbell F.C. Vitamin D3 suppresses morphological evolution of the cribriform cancerous phenotype.Oncotarget. 2016; 7: 49042-49064Crossref PubMed Scopus (7) Google Scholar, 11Deevi R.K. Javadi A. McClements J. Vohhodina J. Savage K. Loughrey M.B. Evergren E. Campbell F.C. Protein kinase C zeta suppresses low- or high-grade colorectal cancer (CRC) phenotypes by interphase centrosome anchoring.J Pathol. 2018; 244: 445-459Crossref PubMed Scopus (4) Google Scholar and associated translational studies.10Deevi R. McClements J. McCloskey K.D. Fatehullah A. Tkocz D. Javadi A. Higginson R. Marsh Durban V. Jansen M. Clarke A. Loughrey M.B. Campbell F.C. Vitamin D3 suppresses morphological evolution of the cribriform cancerous phenotype.Oncotarget. 2016; 7: 49042-49064Crossref PubMed Scopus (7) Google Scholar, 11Deevi R.K. Javadi A. McClements J. Vohhodina J. Savage K. Loughrey M.B. Evergren E. Campbell F.C. Protein kinase C zeta suppresses low- or high-grade colorectal cancer (CRC) phenotypes by interphase centrosome anchoring.J Pathol. 2018; 244: 445-459Crossref PubMed Scopus (4) Google Scholar Signaling nodes converge diverse molecular inputs to yield morphologically homogeneous changes12Gerlinger M. Rowan A.J. Horswell S. Larkin J. Endesfelder D. Gronroos E. Martinez P. Matthews N. Stewart A. Tarpey P. Varela I. Phillimore B. Begum S. McDonald N.Q. Butler A. Jones D. Raine K. Latimer C. Santos C.R. Nohadani M. Eklund A.C. Spencer-Dene B. Clark G. Pickering L. Stamp G. Gore M. Szallasi Z. Downward J. Futreal P.A. Swanton C. Intratumor heterogeneity and branched evolution revealed by multiregion sequencing.N Engl J Med. 2012; 366: 883-892Crossref PubMed Scopus (5759) Google Scholar or, conversely, drive morphologic heterogeneity.1Heng Y.J. Lester S.C. Tse G.M. Factor R.E. Allison K.H. Collins L.C. Chen Y.Y. Jensen K.C. Johnson N.B. Jeong J.C. Punjabi R. Shin S.J. Singh K. Krings G. Eberhard D.A. Tan P.H. Korski K. Waldman F.M. Gutman D.A. Sanders M. Reis-Filho J.S. Flanagan S.R. Gendoo D.M. Chen G.M. Haibe-Kains B. Ciriello G. Hoadley K.A. Perou C.M. Beck A.H. The molecular basis of breast cancer pathological phenotypes.J Pathol. 2017; 241: 375-391Crossref PubMed Scopus (75) Google Scholar Principles outlined may provide insight into CRC molecular subtype biology,13Guinney J. Dienstmann R. Wang X. de Reynies A. Schlicker A. Soneson C. et al.The consensus molecular subtypes of colorectal cancer.Nat Med. 2015; 21: 1350-1356Crossref PubMed Scopus (2692) Google Scholar guide tumor organoid studies,14van de Wetering M. Francies H.E. Francis J.M. Bounova G. Iorio F. Pronk A. et al.Prospective derivation of a living organoid biobank of colorectal cancer patients.Cell. 2015; 161: 933-945Abstract Full Text Full Text PDF PubMed Scopus (1361) Google Scholar and aid next-generation multiplexed imaging of tumor sections.15Giesen C. Wang H.A. Schapiro D. Zivanovic N. Jacobs A. Hattendorf B. Schuffler P.J. Grolimund D. Buhmann J.M. Brandt S. Varga Z. Wild P.J. Gunther D. Bodenmiller B. Highly multiplexed imaging of tumor tissues with subcellular resolution by mass cytometry.Nat Methods. 2014; 11: 417-422Crossref PubMed Scopus (986) Google Scholar The phenome of any tumor represents the entirety of its observable traits. In CRC, these have been intuitively categorized according to apparent biological perturbations and include the following (Figure 1): i) cell cycle phenotypes such as mitotic indices and aberrant mitotic figures16Thunnissen F.B. Ambergen A.W. Koss M. Travis W.D. O'Leary T.J. Ellis I.O. Mitotic counting in surgical pathology: sampling bias, heterogeneity and statistical uncertainty.Histopathology. 2001; 39: 1-8Crossref PubMed Scopus (35) Google Scholar; ii) nuclear configurations, including size, shape, and pleomorphism17Resch A. Harbaum L. Pollheimer M.J. Kornprat P. Lindtner R.A. Langner C. Inclusion of cytological features in tumor grading improves prognostic stratification of patients with colorectal cancer.Int J Colorectal Dis. 2016; 31: 535-541Crossref PubMed Scopus (5) Google Scholar; iii) cell death indices, including apoptosis, necrosis, or necroptosis; iv) functional specialization, including expression of metalloproteinases or other secreted proteins18Stenzinger A. Wittschieber D. von Winterfeld M. Goeppert B. Kamphues C. Weichert W. Dietel M. Rabien A. Klauschen F. High extracellular matrix metalloproteinase inducer/CD147 expression is strongly and independently associated with poor prognosis in colorectal cancer.Hum Pathol. 2012; 43: 1471-1481Crossref PubMed Scopus (29) Google Scholar; v) cell membrane perturbations such as extensions into the stroma known as podia,19Prall F. Ostwald C. High-degree tumor budding and podia-formation in sporadic colorectal carcinomas with K-ras gene mutations.Hum Pathol. 2007; 38: 1696-1702Crossref PubMed Scopus (48) Google Scholar intracellular apical membrane (AM) vacuoles in signet-ring cancers,20Compton C.C. Colorectal carcinoma: diagnostic, prognostic, and molecular features.Mod Pathol. 2003; 16: 376-388Crossref PubMed Scopus (306) Google Scholar and reversed membrane polarity21Cserni G. Reversed polarity of the glandular epithelial cells in micropapillary carcinoma of the large intestine and the EMA/MUC1 immunostain.Pathology. 2014; 46: 527-532Abstract Full Text PDF PubMed Scopus (11) Google Scholar; vi) multicellular arrangements, including cribriform,10Deevi R. McClements J. McCloskey K.D. Fatehullah A. Tkocz D. Javadi A. Higginson R. Marsh Durban V. Jansen M. Clarke A. Loughrey M.B. Campbell F.C. Vitamin D3 suppresses morphological evolution of the cribriform cancerous phenotype.Oncotarget. 2016; 7: 49042-49064Crossref PubMed Scopus (7) Google Scholar micropapillary21Cserni G. Reversed polarity of the glandular epithelial cells in micropapillary carcinoma of the large intestine and the EMA/MUC1 immunostain.Pathology. 2014; 46: 527-532Abstract Full Text PDF PubMed Scopus (11) Google Scholar or high-grade CRC morphology,11Deevi R.K. Javadi A. McClements J. Vohhodina J. Savage K. Loughrey M.B. Evergren E. Campbell F.C. Protein kinase C zeta suppresses low- or high-grade colorectal cancer (CRC) phenotypes by interphase centrosome anchoring.J Pathol. 2018; 244: 445-459Crossref PubMed Scopus (4) Google Scholar, 22Jass J.R. Classification of colorectal cancer based on correlation of clinical, morphological and molecular features.Histopathology. 2007; 50: 113-130Crossref PubMed Scopus (1098) Google Scholar tumor budding and poorly differentiated clusters of cancer cells out with glandular structures23Ueno H. Kajiwara Y. Shimazaki H. Shinto E. Hashiguchi Y. Nakanishi K. Maekawa K. Katsurada Y. Nakamura T. Mochizuki H. Yamamoto J. Hase K. New criteria for histologic grading of colorectal cancer.Am J Surg Pathol. 2012; 36: 193-201Crossref PubMed Scopus (146) Google Scholar; and vii) invasion patterns described as infiltrative or expansive.22Jass J.R. Classification of colorectal cancer based on correlation of clinical, morphological and molecular features.Histopathology. 2007; 50: 113-130Crossref PubMed Scopus (1098) Google Scholar For more than a century, these variables have been assessed for cancer diagnosis and also enable prognostic stratification or prediction of metastatic behavior. For example, both signet-ring and micropapillary CRC morphologies are associated with transcelomic metastatic dissemination and poor clinical outlook.24Hugen N. van de Velde C.J. de Wilt J.H. Nagtegaal I.D. Metastatic pattern in colorectal cancer is strongly influenced by histological subtype.Ann Oncol. 2014; 25: 651-657Abstract Full Text Full Text PDF PubMed Scopus (284) Google Scholar Co-dependencies among histopathologic phenotypes contribute to morphologic complexity. For instance, breakdown of CRC gland morphology associates with escape of cancer cells or clusters,23Ueno H. Kajiwara Y. Shimazaki H. Shinto E. Hashiguchi Y. Nakanishi K. Maekawa K. Katsurada Y. Nakamura T. Mochizuki H. Yamamoto J. Hase K. New criteria for histologic grading of colorectal cancer.Am J Surg Pathol. 2012; 36: 193-201Crossref PubMed Scopus (146) Google Scholar micropapillary morphology associates with reversed membrane polarity,21Cserni G. Reversed polarity of the glandular epithelial cells in micropapillary carcinoma of the large intestine and the EMA/MUC1 immunostain.Pathology. 2014; 46: 527-532Abstract Full Text PDF PubMed Scopus (11) Google Scholar and podia formation associates with tumor budding19Prall F. Ostwald C. High-degree tumor budding and podia-formation in sporadic colorectal carcinomas with K-ras gene mutations.Hum Pathol. 2007; 38: 1696-1702Crossref PubMed Scopus (48) Google Scholar and infiltrative invasion patterns.19Prall F. Ostwald C. High-degree tumor budding and podia-formation in sporadic colorectal carcinomas with K-ras gene mutations.Hum Pathol. 2007; 38: 1696-1702Crossref PubMed Scopus (48) Google Scholar Despite the system noise due to complexity and inter- and intra-observer variation, histologic grading based on expert assessment of collective phenotype patterns provides a well-established means of prognostic stratification.22Jass J.R. Classification of colorectal cancer based on correlation of clinical, morphological and molecular features.Histopathology. 2007; 50: 113-130Crossref PubMed Scopus (1098) Google Scholar To understand cancer phenotype evolution, it is necessary to unravel the molecular framework of normal tissue homeostasis. Core processes of physiological tissue assembly include establishment of cell shape, symmetric or asymmetric division,25Potten C.S. Loeffler M. Stem cells: attributes, cycles, spirals, pitfalls and uncertainties. Lessons for and from the crypt.Development. 1990; 110: 1001-1020Crossref PubMed Google Scholar junction formation,26Campbell H.K. Maiers J.L. DeMali K.A. Interplay between tight junctions & adherens junctions.Exp Cell Res. 2017; 358: 39-44Crossref PubMed Scopus (157) Google Scholar stem cell or lineage commitment,27Sattar A. Robson S.C. Patel H.R. Angus B. Campbell F.C. Expression of growth regulatory genes in a SCID mouse-human model of intestinal epithelial regeneration.J Pathol. 1999; 187: 229-236Crossref PubMed Scopus (14) Google Scholar and formation of simple multicellular patterns.5Lechler T. Fuchs E. Asymmetric cell divisions promote stratification and differentiation of mammalian skin.Nature. 2005; 437: 275-280Crossref PubMed Scopus (763) Google Scholar, 6Jaffe A.B. Kaji N. Durgan J. Hall A. Cdc42 controls spindle orientation to position the apical surface during epithelial morphogenesis.J Cell Biol. 2008; 183: 625-633Crossref PubMed Scopus (268) Google Scholar, 7Bryant D.M. Mostov K.E. From cells to organs: building polarized tissue.Nat Rev Mol Cell Biol. 2008; 9: 887-901Crossref PubMed Scopus (585) Google Scholar Subsequent sculpting by epithelial folding28Wang Y.C. Khan Z. Kaschube M. Wieschaus E.F. Differential positioning of adherens junctions is associated with initiation of epithelial folding.Nature. 2012; 484: 390-393Crossref PubMed Scopus (119) Google Scholar or movements induce more complex tissue architecture. Studies in biological model systems have revealed functional interdependence of these processes8Magudia K. Lahoz A. Hall A. K-Ras and B-Raf oncogenes inhibit colon epithelial polarity establishment through up-regulation of c-myc.J Cell Biol. 2012; 198: 185-194Crossref PubMed Scopus (42) Google Scholar, 9Bryant D.M. Roignot J. Datta A. Overeem A.W. Kim M. Yu W. Peng X. Eastburn D.J. Ewald A.J. Werb Z. Mostov K.E. A molecular switch for the orientation of epithelial cell polarization.Dev Cell. 2014; 31: 171-187Abstract Full Text Full Text PDF PubMed Scopus (132) Google Scholar, 29Morais-de-Sa E. Mirouse V. St Johnston D. aPKC phosphorylation of Bazooka defines the apical/lateral border in Drosophila epithelial cells.Cell. 2010; 141: 509-523Abstract Full Text Full Text PDF PubMed Scopus (211) Google Scholar, 30Martin-Belmonte F. Gassama A. Datta A. Yu W. Rescher U. Gerke V. Mostov K. PTEN-mediated apical segregation of phosphoinositides controls epithelial morphogenesis through Cdc42.Cell. 2007; 128: 383-397Abstract Full Text Full Text PDF PubMed Scopus (561) Google Scholar, 31Jagan I. Fatehullah A. Deevi R.K. Bingham V. Campbell F.C. Rescue of glandular dysmorphogenesis in PTEN-deficient colorectal cancer epithelium by PPARgamma-targeted therapy.Oncogene. 2013; 32: 1305-1315Crossref PubMed Scopus (16) Google Scholar, 32Jagan I.C. Deevi R.K. Fatehullah A. Topley R. Eves J. Stevenson M. Loughrey M. Arthur K. Campbell F.C. PTEN phosphatase-independent maintenance of glandular morphology in a predictive colorectal cancer model system.Neoplasia. 2013; 15: 1218-1230Crossref PubMed Scopus (22) Google Scholar and provide insight into evolutionary histories of common cancers. Here, we briefly review integrated processes of tissue formation, whereas accompanying references provide more in-depth mechanistic detail. Transition of a single cell to a cooperative complex of multicellular organs is the basis of all higher life.33Zernicka-Goetz M. Patterning of the embryo: the first spatial decisions in the life of a mouse.Development. 2002; 129: 815-829PubMed Google Scholar An essential milestone in this process is the internal reorganization of subcellular components that precedes the first division of the first cell (the fertilized oocyte or zygote). Conserved complexes of mutually antagonistic anterior and posterior polarity determinants, including protein kinase C ζ (PRKCζ), partitioning defective (PARD)3, PARD6 (anterior), and PARD1 and PARD2 (posterior) become redistributed to distinct regions or poles within the cell cortex (periphery)34Motegi F. Seydoux G. The PAR network: redundancy and robustness in a symmetry-breaking system.Philos Trans R Soc Lond B Biol Sci. 2013; 368: 20130010Crossref PubMed Scopus (61) Google Scholar, 35Nance J. Zallen J.A. Elaborating polarity: PAR proteins and the cytoskeleton.Development. 2011; 138: 799-809Crossref PubMed Scopus (120) Google Scholar, 36Spira F. Cuylen-Haering S. Mehta S. Samwer M. Reversat A. Verma A. Oldenbourg R. Sixt M. Gerlich D.W. Cytokinesis in vertebrate cells initiates by contraction of an equatorial actomyosin network composed of randomly oriented filaments.Elife. 2017; 6: e30867Crossref PubMed Scopus (30) Google Scholar, 37Glotzer M. The 3Ms of central spindle assembly: microtubules, motors and MAPs.Nat Rev Mol Cell Biol. 2009; 10: 9-20Crossref PubMed Scopus (277) Google Scholar, 38Bananis E. Nath S. Gordon K. Satir P. Stockert R.J. Murray J.W. Wolkoff A.W. Microtubule-dependent movement of late endocytic vesicles in vitro: requirements for Dynein and Kinesin.Mol Biol Cell. 2004; 15: 3688-3697Crossref PubMed Scopus (93) Google Scholar, 39Munjal A. Lecuit T. Actomyosin networks and tissue morphogenesis.Development. 2014; 141: 1789-1793Crossref PubMed Scopus (138) Google Scholar (Figure 2, A and B). Such spatial separation of polarity determinants is mediated by actomyosin and other motor protein activity,40Gotta M. Abraham M.C. Ahringer J. CDC-42 controls early cell polarity and spindle orientation in C. elegans.Curr Biol. 2001; 11: 482-488Abstract Full Text Full Text PDF PubMed Scopus (175) Google Scholar activated by the Rho GTPase family41Kay A.J. Hunter C.P. CDC-42 regulates PAR protein localization and function to control cellular and embryonic polarity in C. elegans.Curr Biol. 2001; 11: 474-481Abstract Full Text Full Text PDF PubMed Scopus (123) Google Scholar and driven by GTP-based energy sources.42Karsenti E. Self-organization in cell biology: a brief history.Nat Rev Mol Cell Biol. 2008; 9: 255-262Crossref PubMed Scopus (349) Google Scholar Spatial organization machinery, including antagonistic polarity complexes,34Motegi F. Seydoux G. The PAR network: redundancy and robustness in a symmetry-breaking system.Philos Trans R Soc Lond B Biol Sci. 2013; 368: 20130010Crossref PubMed Scopus (61) Google Scholar cortical flow,39Munjal A. Lecuit T. Actomyosin networks and tissue morphogenesis.Development. 2014; 141: 1789-1793Crossref PubMed Scopus (138) Google Scholar and Rho GTPase signaling,41Kay A.J. Hunter C.P. CDC-42 regulates PAR protein localization and function to control cellular and embryonic polarity in C. elegans.Curr Biol. 2001; 11: 474-481Abstract Full Text Full Text PDF PubMed Scopus (123) Google Scholar is conserved with some important modifications in cells of all tissues with the capacity for self-renewal (renewal tissues). Fundamental processes for sharing genetic material between daughter cells, determination of cell fate, and assembly of distinct functional cell lineages into specific tissues and organs are controlled by transitions between asymmetric and symmetric cell division.43Harandi O.F. Ambros V.R. Control of stem cell self-renewal and differentiation by the heterochronic genes and the cellular asymmetry machinery in Caenorhabditis elegans.Proc Natl Acad Sci U S A. 2015; 112: E287-E296Crossref PubMed Scopus (26) Google Scholar This remarkable plasticity is regulated by cortical PARD proteins,44Wu J.C. Rose L.S. PAR-3 and PAR-1 inhibit LET-99 localization to generate a cortical band important for spindle positioning in Caenorhabditis elegans embryos.Mol Biol Cell. 2007; 18: 4470-4482Crossref PubMed Scopus (27) Google Scholar microtubule (MT), and actin cytoskeleton dynamics.45St Johnston D. Sanson B. Epithelial polarity and morphogenesis.Curr Opin Cell Biol. 2011; 23: 540-546Crossref PubMed Scopus (106) Google Scholar This crosstalk provides a framework for sequential processes of internal cell reorganization, mitotic spindle construction and orientation, segregation of the genome and cell fate determinants, positioning of intercellular junctions, specialized cell membranes, polarized cell topology, and multicellular patterning during tissue assembly. Like the zygote, adult cells remodel their actin and MT cytoskeletons in preparation for mitosis. Actin-dependent mechanisms generate the forces required for cell stiffening and rounding, movement of proteins within the cortex,46Rosenblatt J. Cramer L.P. Baum B. McGee K.M. Myosin II-dependent cortical movement is required for centrosome separation and positioning during mitotic spindle assembly.Cell. 2004; 117: 361-372Abstract Full Text Full Text PDF PubMed Scopus (216) Google Scholar and positioning of cues for astral MT binding and centrosome stabilization.11Deevi R.K. Javadi A. McClements J. Vohhodina J. Savage K. Loughrey M.B. Evergren E. Campbell F.C. Protein kinase C zeta suppresses low- or high-grade colorectal cancer (CRC) phenotypes by interphase centrosome anchoring.J Pathol. 2018; 244: 445-459Crossref PubMed Scopus (4) Google Scholar, 47Hebert A.M. DuBoff B. Casaletto J.B. Gladden A.B. McClatchey A.I. Merlin/ERM proteins establish cortical asymmetry and centrosome position.Genes Dev. 2012; 26: 2709-2723Crossref PubMed Scopus (49) Google Scholar These processes can also promote clustering of extra centrosomes11Deevi R.K. Javadi A. McClements J. Vohhodina J. Savage K. Loughrey M.B. Evergren E. Campbell F.C. Protein kinase C zeta suppresses low- or high-grade colorectal cancer (CRC) phenotypes by interphase centrosome anchoring.J Pathol. 2018; 244: 445-459Crossref PubMed Scopus (4) Google Scholar, 47Hebert A.M. DuBoff B. Casaletto J.B. Gladden A.B. McClatchey A.I. Merlin/ERM proteins establish cortical asymmetry and centrosome position.Genes Dev. 2012; 26: 2709-2723Crossref PubMed Scopus (49) Google Scholar that are common in cancer cells.48Ganem N.J. Godinho S.A. Pellman D. A mechanism linking extra centrosomes to chromosomal instability.Nature. 2009; 460: 278-282Crossref PubMed Scopus (1020) Google Scholar Transmission of the genome to daughter cells involves assembly of a bipolar mitotic spindle from two centrosomes, MTs, DNA linkages, appropriately positioned motor proteins, and connections to the cell cortex36Spira F. Cuylen-Haering S. Mehta S. Samwer M. Reversat A. Verma A. Oldenbourg R. Sixt M. Gerlich D.W. Cytokinesis in vertebrate cells initiates by contraction of an equatorial actomyosin network composed of randomly oriented filaments.Elife. 2017; 6: e30867Crossref PubMed Scopus (30) Google Scholar (Figure 2, C and D). Binding of astral MTs to localized cues within the cortex anchors centrosomes during mitotic spindle formation. Once fully assembled, the mitotic spindle is orientated by an equilibrium maintained between functionally antagonistic polarity regulators.49Durgan J. Kaji N. Jin D. Hall A. Par6B and atypical PKC regulate mitotic spindle orientation during epithelial morphogenesis.J Biol Chem. 2011; 286: 12461-12474Crossref PubMed Scopus (102) Google Scholar Antagonism between PRKCζ and PARD1 regulates localization of PARD329Morais-de-Sa E. Mirouse V. St Johnston D. aPKC phosphorylation of Bazooka defines the apical/lateral border in Drosophila epithelial cells.Cell. 2010; 141: 509-523Abstract Full Text Full Text PDF PubMed Scopus (211) Google Scholar that controls the spindle orientation protein, G protein signaling modulator 2 (also known as LGN for leu-gly-asn).50Williams S.E. Ratliff L.A. Postiglione M.P. Knoblich J.A. Fuchs E. Par3-mInsc and Galphai3 cooperate to promote oriented epidermal cell divisions through LGN.Nat Cell Biol. 2014; 16: 758-769Crossref PubMed Scopus (96) Google Scholar These mechanisms control MT-mediated pulling forces for appropriate spindle alignment.50Williams S.E. Ratliff L.A. Postiglione M.P. Knoblich J.A. Fuchs E. Par3-mInsc and Galphai3 cooperate to promote oriented epidermal cell divisions through LGN.Nat Cell Biol. 20" @default.
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• W2884353479 date "2018-09-01" @default.
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• W2884353479 title "Mechanistic Insights into Colorectal Cancer Phenomics from Fundamental and Organotypic Model Studies" @default.
• W2884353479 cites W1483496013 @default.
• W2884353479 cites W1565417674 @default.
• W2884353479 cites W1741548448 @default.
• W2884353479 cites W1934094702 @default.
• W2884353479 cites W1967674619 @default.
• W2884353479 cites W1968407767 @default.
• W2884353479 cites W1968877074 @default.
• W2884353479 cites W1972204116 @default.
• W2884353479 cites W1976923948 @default.
• W2884353479 cites W1978968660 @default.
• W2884353479 cites W1980226777 @default.
• W2884353479 cites W1982645824 @default.
• W2884353479 cites W1984163925 @default.
• W2884353479 cites W1985817016 @default.
• W2884353479 cites W1990188178 @default.
• W2884353479 cites W1990671797 @default.
• W2884353479 cites W2002513358 @default.
• W2884353479 cites W2002897207 @default.
• W2884353479 cites W2006989477 @default.
• W2884353479 cites W2007354846 @default.
• W2884353479 cites W2012077408 @default.
• W2884353479 cites W2012282535 @default.
• W2884353479 cites W2014821302 @default.
• W2884353479 cites W2017823697 @default.
• W2884353479 cites W2018440302 @default.
• W2884353479 cites W2019237297 @default.
• W2884353479 cites W2019761859 @default.
• W2884353479 cites W2021468144 @default.
• W2884353479 cites W2023072510 @default.
• W2884353479 cites W2023649138 @default.
• W2884353479 cites W2030945062 @default.
• W2884353479 cites W2031285753 @default.
• W2884353479 cites W2033751993 @default.
• W2884353479 cites W2034653929 @default.
• W2884353479 cites W2036639309 @default.
• W2884353479 cites W2036736619 @default.
• W2884353479 cites W2036833378 @default.
• W2884353479 cites W2037330590 @default.
• W2884353479 cites W2041677910 @default.
• W2884353479 cites W2045337571 @default.
• W2884353479 cites W2045427414 @default.
• W2884353479 cites W2045792291 @default.
• W2884353479 cites W2051477353 @default.
• W2884353479 cites W2053129129 @default.
• W2884353479 cites W2054224885 @default.
• W2884353479 cites W2054447190 @default.
• W2884353479 cites W2070599389 @default.
• W2884353479 cites W2071885493 @default.
• W2884353479 cites W2072895299 @default.
• W2884353479 cites W2073557891 @default.
• W2884353479 cites W2074906952 @default.
• W2884353479 cites W2076457965 @default.
• W2884353479 cites W2085963386 @default.
• W2884353479 cites W2085971602 @default.
• W2884353479 cites W2087615949 @default.
• W2884353479 cites W2093531978 @default.
• W2884353479 cites W2098286938 @default.
• W2884353479 cites W2099378655 @default.
• W2884353479 cites W2099936921 @default.
• W2884353479 cites W2101493293 @default.
• W2884353479 cites W2103547637 @default.
• W2884353479 cites W2108643617 @default.
• W2884353479 cites W2109219393 @default.
• W2884353479 cites W2111044431 @default.
• W2884353479 cites W2112966482 @default.
• W2884353479 cites W2123787611 @default.
• W2884353479 cites W2126070753 @default.
• W2884353479 cites W2126477220 @default.
• W2884353479 cites W2132566055 @default.
• W2884353479 cites W2133771242 @default.
• W2884353479 cites W2134590240 @default.
• W2884353479 cites W2136808082 @default.
• W2884353479 cites W2139348176 @default.
• W2884353479 cites W2142451800 @default.
• W2884353479 cites W2147399984 @default.
• W2884353479 cites W2148440651 @default.
• W2884353479 cites W2148459495 @default.
• W2884353479 cites W2148586791 @default.
• W2884353479 cites W2148883613 @default.
• W2884353479 cites W2150575159 @default.
• W2884353479 cites W2151711338 @default.
• W2884353479 cites W2154192657 @default.
• W2884353479 cites W2164985111 @default.
• W2884353479 cites W2166937493 @default.
• W2884353479 cites W2167412334 @default.
• W2884353479 cites W2168901267 @default.
• W2884353479 cites W2171977041 @default.

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