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Modulation of metastatic propensity of triple-negative breast cancer cells harboring p53 mutations

Thursday, November 07, 2013 — Poster Session II

12:00 p.m. – 2:00 p.m.

FAES Academic Center (Upper-Level Terrace)




  • B.L. Morrison
  • F. Bernal


The mutation of p53 is critical for the increased metastatic potential of triple-negative breast cancer (TNBC). As such, it is essential not only to understand the mechanisms underlying the functional implications of p53 mutation, but also to identify ways to regulate their impact in cancer cell physiology. I have found that a hydrocarbon stapled p53 transactivation domain peptide (SAH-p53) designed to disrupt the interaction with its negative regulators HDM2 and HDMX retains its function in cells harboring a mutant TP53. A common gain-of-function activity of the mutant p53 protein (mtp53) is the enhancement of cell migration and invasion. I have found that SAH-p53 inhibits the migration and invasion of MDA-MB-231 cells (mtp53) at a sub-lethal dose. This effect was accompanied by an alteration in actin stress fiber formation, a decrease in the levels of actin polymerization proteins, and dissolution of focal adhesions. Moreover, a decrease in the total levels of EGFR and integrin beta1 suggests a defect in receptor recycling, a process required for cell migration. 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.

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