Novel role of PELP1 in regulating chemotherapy response in mutant p53-expressing triple negative breast cancer cells

Breast Cancer Research and Treatment
Samaya R KrishnanR K Vadlamudi

Abstract

Triple-negative breast cancer (TNBC), the most aggressive breast cancer subtype, occurs in younger women and is associated with poor prognosis. Gain-of-function mutations in TP53 are a frequent occurrence in TNBC and have been demonstrated to repress apoptosis and up-regulate cell cycle progression. Even though TNBC responds to initial chemotherapy, resistance to chemotherapy develops and is a major clinical problem. Tumor recurrence eventually occurs and most patients die from their disease. An urgent need exists to identify molecular-targeted therapies that can enhance chemotherapy response. In the present study, we report that targeting PELP1, an oncogenic co-regulator molecule, could enhance the chemotherapeutic response of TNBC through the inhibition of cell cycle progression and activation of apoptosis. We demonstrate that PELP1 interacts with MTp53, regulates its recruitment, and alters epigenetic marks at the target gene promoters. PELP1 knockdown reduced MTp53 target gene expression, resulting in decreased cell survival and increased apoptosis upon genotoxic stress. Mechanistic studies revealed that PELP1 depletion contributes to increased stability of E2F1, a transcription factor that regulates both cell cycle and apo...Continue Reading

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Citations

Mar 22, 2016·Gene·Gangadhara Reddy Sareddy, Ratna K Vadlamudi
Jun 3, 2017·Archives of Pathology & Laboratory Medicine·Yan PengPing Tang
Dec 25, 2019·Molecular Carcinogenesis·Yiliao LuoRatna K Vadlamudi
Apr 21, 2020·Neuro-oncology Advances·Gangadhara R SareddyRatna K Vadlamudi
Apr 14, 2016·Biochemical Society Transactions·Lydia Aschauer, Patricia A J Muller
Dec 11, 2019·International Journal of Molecular Sciences·Yan SteinRonit Aloni-Grinstein
May 10, 2017·Journal of Neuroendocrinology·R ThakkarD Brann
Jan 29, 2021·Frontiers in Oncology·Dishari GhatakSusanta Roychoudhury

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