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TRPML1 REGULATES PROSTATE CANCER CELL PROLIFERATION THROUGH THE MODULATION OF OXIDATIVE STRESS AND CELL CYCLE

Date

2018-09-04T11:44:08Z

Authors

Sterea, Andra Mihaela

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Abstract

Prostate cancer (PCa) represents a multifactorial and complex disease affecting thousands of men each year. Although the prognosis of PCa is improving, limitations in early diagnosis pose a challenge for the effective treatment of patients with late stages of the disease. Research is now focusing on targeting ion channels as a means of delaying the progression of PCa in patients who do not respond to traditional therapies. One potential target is the ion channel TRPML1 whose function mediates cellular bioenergetics. Here, we demonstrate that TRPML1 is overexpressed in PCa cells and its downregulation decreases cell proliferation. At the molecular level, the loss of TRPML1 impairs autophagy resulting in the accumulation of free radicals, ultimately leading to DNA damage and cell cycle arrest. Our data suggests an important role for TRPML1 in the maintenance of PCa cell proliferation and its potential as a novel therapeutic target for the treatment of PCa.

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Keywords

Prostate Cancer, TRPML1, Targeted therapy, Lysosomes, Autophagy, Ion channels

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