Matches in SemOpenAlex for { <https://semopenalex.org/work/W2160670827> ?p ?o ?g. }
- W2160670827 abstract "The normal process of epithelial mesenchymal transition (EMT) is subverted by carcinoma cells to facilitate metastatic spread. Cancer cells rarely undergo a full conversion to the mesenchymal phenotype, and instead adopt positions along the epithelial-mesenchymal axis, a propensity we refer to as epithelial mesenchymal plasticity (EMP). EMP is associated with increased risk of metastasis in breast cancer and consequent poor prognosis. Drivers towards the mesenchymal state in malignant cells include growth factor stimulation or exposure to hypoxic conditions.We have examined EMP in two cell line models of breast cancer: the PMC42 system (PMC42-ET and PMC42-LA sublines) and MDA-MB-468 cells. Transition to a mesenchymal phenotype was induced across all three cell lines using epidermal growth factor (EGF) stimulation, and in MDA-MB-468 cells by hypoxia. We used RNA sequencing to identify gene expression changes that occur as cells transition to a more-mesenchymal phenotype, and identified the cell signalling pathways regulated across these experimental systems. We then used inhibitors to modulate signalling through these pathways, verifying the conclusions of our transcriptomic analysis.We found that EGF and hypoxia both drive MDA-MB-468 cells to phenotypically similar mesenchymal states. Comparing the transcriptional response to EGF and hypoxia, we have identified differences in the cellular signalling pathways that mediate, and are influenced by, EMT. Significant differences were observed for a number of important cellular signalling components previously implicated in EMT, such as HBEGF and VEGFA. We have shown that EGF- and hypoxia-induced transitions respond differently to treatment with chemical inhibitors (presented individually and in combinations) in these breast cancer cells. Unexpectedly, MDA-MB-468 cells grown under hypoxic growth conditions became even more mesenchymal following exposure to certain kinase inhibitors that prevent growth-factor induced EMT, including the mTOR inhibitor everolimus and the AKT1/2/3 inhibitor AZD5363.While resulting in a common phenotype, EGF and hypoxia induced subtly different signalling systems in breast cancer cells. Our findings have important implications for the use of kinase inhibitor-based therapeutic interventions in breast cancers, where these heterogeneous signalling landscapes will influence the therapeutic response." @default.
- W2160670827 created "2016-06-24" @default.
- W2160670827 creator A5000736900 @default.
- W2160670827 creator A5002033152 @default.
- W2160670827 creator A5004957581 @default.
- W2160670827 creator A5018252802 @default.
- W2160670827 creator A5029344208 @default.
- W2160670827 creator A5033306158 @default.
- W2160670827 creator A5048486605 @default.
- W2160670827 creator A5049570974 @default.
- W2160670827 creator A5055292298 @default.
- W2160670827 creator A5061492074 @default.
- W2160670827 creator A5083478373 @default.
- W2160670827 date "2015-05-15" @default.
- W2160670827 modified "2023-10-02" @default.
- W2160670827 title "Stimulus-dependent differences in signalling regulate epithelial-mesenchymal plasticity and change the effects of drugs in breast cancer cell lines" @default.
- W2160670827 cites W1497663772 @default.
- W2160670827 cites W1521488064 @default.
- W2160670827 cites W1533487512 @default.
- W2160670827 cites W1662062786 @default.
- W2160670827 cites W1907933208 @default.
- W2160670827 cites W1957632644 @default.
- W2160670827 cites W1963888992 @default.
- W2160670827 cites W1964081206 @default.
- W2160670827 cites W1964847767 @default.
- W2160670827 cites W1965206987 @default.
- W2160670827 cites W1969938369 @default.
- W2160670827 cites W1971303929 @default.
- W2160670827 cites W1971607079 @default.
- W2160670827 cites W1973932751 @default.
- W2160670827 cites W1980623424 @default.
- W2160670827 cites W1985339653 @default.
- W2160670827 cites W1988055795 @default.
- W2160670827 cites W1988106671 @default.
- W2160670827 cites W1993253909 @default.
- W2160670827 cites W1994277957 @default.
- W2160670827 cites W1995507236 @default.
- W2160670827 cites W1998071315 @default.
- W2160670827 cites W1999082557 @default.
- W2160670827 cites W2000767539 @default.
- W2160670827 cites W2002418457 @default.
- W2160670827 cites W2003380944 @default.
- W2160670827 cites W2004774166 @default.
- W2160670827 cites W2004946118 @default.
- W2160670827 cites W2010813562 @default.
- W2160670827 cites W2011033752 @default.
- W2160670827 cites W2013558607 @default.
- W2160670827 cites W2014691022 @default.
- W2160670827 cites W2022480285 @default.
- W2160670827 cites W2023427658 @default.
- W2160670827 cites W2025486904 @default.
- W2160670827 cites W2025872894 @default.
- W2160670827 cites W2029178847 @default.
- W2160670827 cites W2030899725 @default.
- W2160670827 cites W2040614639 @default.
- W2160670827 cites W2042198997 @default.
- W2160670827 cites W2044066240 @default.
- W2160670827 cites W2044702943 @default.
- W2160670827 cites W2044862408 @default.
- W2160670827 cites W2046679772 @default.
- W2160670827 cites W2047172303 @default.
- W2160670827 cites W2051541007 @default.
- W2160670827 cites W2055498399 @default.
- W2160670827 cites W2056513373 @default.
- W2160670827 cites W2057364858 @default.
- W2160670827 cites W2057895115 @default.
- W2160670827 cites W2060099765 @default.
- W2160670827 cites W2063011414 @default.
- W2160670827 cites W2065476976 @default.
- W2160670827 cites W2066441178 @default.
- W2160670827 cites W2067139290 @default.
- W2160670827 cites W2067586338 @default.
- W2160670827 cites W2069887628 @default.
- W2160670827 cites W2070839003 @default.
- W2160670827 cites W2077462602 @default.
- W2160670827 cites W2085312694 @default.
- W2160670827 cites W2088620830 @default.
- W2160670827 cites W2089350319 @default.
- W2160670827 cites W2089605820 @default.
- W2160670827 cites W2090253106 @default.
- W2160670827 cites W2093472132 @default.
- W2160670827 cites W2095510412 @default.
- W2160670827 cites W2096283457 @default.
- W2160670827 cites W2097208900 @default.
- W2160670827 cites W2100669034 @default.
- W2160670827 cites W2101330142 @default.
- W2160670827 cites W2103433388 @default.
- W2160670827 cites W2104843251 @default.
- W2160670827 cites W2105675816 @default.
- W2160670827 cites W2105848821 @default.
- W2160670827 cites W2106000067 @default.
- W2160670827 cites W2106036365 @default.
- W2160670827 cites W2115382934 @default.
- W2160670827 cites W2122637273 @default.
- W2160670827 cites W2124218468 @default.
- W2160670827 cites W2124317989 @default.
- W2160670827 cites W2124342958 @default.
- W2160670827 cites W2124803006 @default.
- W2160670827 cites W2128445526 @default.
- W2160670827 cites W2128472773 @default.