Inducing ferroptosis to impede metastasis by inhibiting the calcium channel TRPC6.

ABSTRACT: We investigated a potential function of transient receptor potential cation channel 6 (TRPC6) in enabling breast cancer cells to resist stimuli that induce ferroptosis. A minority population of quiescent cells was isolated from triple-negative breast cancer (TNBC) cell lines that exhibit increased TRPC6 expression and resistance to ferroptosis compared to proliferating cells. These quiescent cells are also more metastatic than the proliferating cells, supporting the hypothesis that metastasis requires the ability of cells to evade ferroptosis. In pursuit of the mechanism, we discovered that the ability of TRPC6 to repress c-Myc is essential because its repression sustains levels of glutathione that are sufficient to impede ferroptosis. Importantly, treatment of TNBC cells with a TRPC6 inhi

SUBMITTER: Dimitrov BS 

PROVIDER: S-EPMC12746528 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature