Matches in SemOpenAlex for { <https://semopenalex.org/work/W2094304316> ?p ?o ?g. }
Showing items 1 to 88 of
88
with 100 items per page.
- W2094304316 abstract "The mutation of p53 is implicated in the increased metastatic potential of triple-negative (ER—/PR—/Her2—) breast cancer (TNBC). The low survival rates of advanced metastatic cancer make it critical not only to understand the mechanisms underlying the functional implications of p53 mutations, but also to identify ways to regulate their impact in cancer cell physiology. A common gain-of-function activity of the mutant p53 protein is the enhancement of cell migration and invasion. We have found that a hydrocarbon-stapled p53 transactivation domain peptide (SAH-p53) designed to disrupt the interaction with p53 negative regulators HDM2 and HDMX also has the ability to inhibit the interaction between mutant p53 (mtp53) and HDM2/HDMX. In addition, SAH-p53 was found to inhibit the migration and invasion of MDA-MB-231 cells (mtp53), while exhibiting no alteration in their proliferative ability. The capacity of SAH-p53 to inhibit MDA-MB-231 cell migration was not altered in the absence of HDMX, suggesting an alternative mechanism of action for SAH-p53. The propensity of MDA-MB-231 cells to migrate and invade through Matrigel in response to transforming growth factor b (TGF-β), epidermal growth factor (EGF), hepatocyte growth factor (HGF), and platelet-derived growth factor (PDGF) was decreased by treatment with SAH-p53. Furthermore, increased concentrations of these growth factors displayed a synergistic effect with SAH-p53 in the inhibition of cell migration, suggesting cross-talk between receptor signaling and SAH-p53 activity. This effect was accompanied by an alteration in stress fiber formation and dissolution of focal adhesions. While the knockdown of mutant p53 in MDA-MB-231 cells significantly decreased migration on its own, inhibition of migration by SAH-p53 was not seen in the EGFR/p53-null MDA-MB-157 cells, suggesting a need for either the p53 or EGFR protein for the inhibitory activity of SAH-p53. Moreover, a SAH-p53-induced decrease in the total levels of EGFR and integrin beta1, together with alterations in actin stability, suggests a defect in receptor recycling, a process required for cell migration known to be modulated by an interaction between mutant p53 and p63. These data show that the use of the SAH-p53 peptide provides a novel avenue to study the molecular interactions that drive metastatic behavior originated by p53 gain-of-function mutations. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-03-05." @default.
- W2094304316 created "2016-06-24" @default.
- W2094304316 creator A5009044210 @default.
- W2094304316 creator A5080220458 @default.
- W2094304316 creator A5090162798 @default.
- W2094304316 date "2013-12-15" @default.
- W2094304316 modified "2023-09-27" @default.
- W2094304316 title "Abstract P3-03-05: Modulation of the metastatic propensity of triple-negative breast cancer cells harboring p53 mutations" @default.
- W2094304316 doi "https://doi.org/10.1158/0008-5472.sabcs13-p3-03-05" @default.
- W2094304316 hasPublicationYear "2013" @default.
- W2094304316 type Work @default.
- W2094304316 sameAs 2094304316 @default.
- W2094304316 citedByCount "0" @default.
- W2094304316 crossrefType "proceedings-article" @default.
- W2094304316 hasAuthorship W2094304316A5009044210 @default.
- W2094304316 hasAuthorship W2094304316A5080220458 @default.
- W2094304316 hasAuthorship W2094304316A5090162798 @default.
- W2094304316 hasConcept C104317684 @default.
- W2094304316 hasConcept C121608353 @default.
- W2094304316 hasConcept C1292079 @default.
- W2094304316 hasConcept C137738243 @default.
- W2094304316 hasConcept C1491633281 @default.
- W2094304316 hasConcept C170493617 @default.
- W2094304316 hasConcept C180361614 @default.
- W2094304316 hasConcept C2775960820 @default.
- W2094304316 hasConcept C2776362946 @default.
- W2094304316 hasConcept C2776996007 @default.
- W2094304316 hasConcept C2778608917 @default.
- W2094304316 hasConcept C2779438470 @default.
- W2094304316 hasConcept C2780110267 @default.
- W2094304316 hasConcept C2780394083 @default.
- W2094304316 hasConcept C502942594 @default.
- W2094304316 hasConcept C530470458 @default.
- W2094304316 hasConcept C54355233 @default.
- W2094304316 hasConcept C62112901 @default.
- W2094304316 hasConcept C81885089 @default.
- W2094304316 hasConcept C86339819 @default.
- W2094304316 hasConcept C86803240 @default.
- W2094304316 hasConcept C96232424 @default.
- W2094304316 hasConceptScore W2094304316C104317684 @default.
- W2094304316 hasConceptScore W2094304316C121608353 @default.
- W2094304316 hasConceptScore W2094304316C1292079 @default.
- W2094304316 hasConceptScore W2094304316C137738243 @default.
- W2094304316 hasConceptScore W2094304316C1491633281 @default.
- W2094304316 hasConceptScore W2094304316C170493617 @default.
- W2094304316 hasConceptScore W2094304316C180361614 @default.
- W2094304316 hasConceptScore W2094304316C2775960820 @default.
- W2094304316 hasConceptScore W2094304316C2776362946 @default.
- W2094304316 hasConceptScore W2094304316C2776996007 @default.
- W2094304316 hasConceptScore W2094304316C2778608917 @default.
- W2094304316 hasConceptScore W2094304316C2779438470 @default.
- W2094304316 hasConceptScore W2094304316C2780110267 @default.
- W2094304316 hasConceptScore W2094304316C2780394083 @default.
- W2094304316 hasConceptScore W2094304316C502942594 @default.
- W2094304316 hasConceptScore W2094304316C530470458 @default.
- W2094304316 hasConceptScore W2094304316C54355233 @default.
- W2094304316 hasConceptScore W2094304316C62112901 @default.
- W2094304316 hasConceptScore W2094304316C81885089 @default.
- W2094304316 hasConceptScore W2094304316C86339819 @default.
- W2094304316 hasConceptScore W2094304316C86803240 @default.
- W2094304316 hasConceptScore W2094304316C96232424 @default.
- W2094304316 hasLocation W20943043161 @default.
- W2094304316 hasOpenAccess W2094304316 @default.
- W2094304316 hasPrimaryLocation W20943043161 @default.
- W2094304316 hasRelatedWork W1548811629 @default.
- W2094304316 hasRelatedWork W1590055389 @default.
- W2094304316 hasRelatedWork W1604234431 @default.
- W2094304316 hasRelatedWork W2005640766 @default.
- W2094304316 hasRelatedWork W2049011998 @default.
- W2094304316 hasRelatedWork W2066128448 @default.
- W2094304316 hasRelatedWork W2070280275 @default.
- W2094304316 hasRelatedWork W2084245555 @default.
- W2094304316 hasRelatedWork W2147254567 @default.
- W2094304316 hasRelatedWork W2319395364 @default.
- W2094304316 hasRelatedWork W2332707936 @default.
- W2094304316 hasRelatedWork W2333074963 @default.
- W2094304316 hasRelatedWork W2403295708 @default.
- W2094304316 hasRelatedWork W2738637586 @default.
- W2094304316 hasRelatedWork W2808683307 @default.
- W2094304316 hasRelatedWork W2810897738 @default.
- W2094304316 hasRelatedWork W3005397169 @default.
- W2094304316 hasRelatedWork W3083409411 @default.
- W2094304316 hasRelatedWork W3100082769 @default.
- W2094304316 hasRelatedWork W3107396422 @default.
- W2094304316 isParatext "false" @default.
- W2094304316 isRetracted "false" @default.
- W2094304316 magId "2094304316" @default.
- W2094304316 workType "article" @default.