Inducing ferroptosis to impede metastasis by inhibiting the calcium channel TRPC6

ABSTRACT: TRPC6 (transient receptor potential cation channel 6) contributes to the ability of breast cancer cells to persist after chemotherapy. Here, we investigated a potential function of 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 using a p27 reporter. These p27+ cells exhibited increased TRPC6 expression and resistance to ferroptosis compared to the p27- proliferating population. The p27+ cells were also more metastatic than the p27- cells supporting the hypothesis that metastasis requires the ability of cells to evade ferroptosis. In pursuit of the mechanism involved, we discovered that the ability of TRPC6 to repress c-Myc is essential because repression of c-Myc sustains levels of glutathione that are sufficient to impede ferroptosis. Importantly, treatment of TNBC cells with a TRPC6 inhibitor reduced metastasis significantly, an effect that was mitigated by liproxstatin-1 treatment. These results support the hypothesis that a sub-population of TNBC cells characterized by TRPC6 expression has the potential to form metastases by evading ferroptosis.

ORGANISM(S): Homo sapiens

PROVIDER: GSE296239 | GEO | 2026/01/12

REPOSITORIES: GEO