2. Academic Validation
  3. Inducing ferroptosis to impede metastasis by inhibiting the calcium channel TRPC6

Inducing ferroptosis to impede metastasis by inhibiting the calcium channel TRPC6

  • Cell Rep. 2025 Nov 25;44(11):116543. doi: 10.1016/j.celrep.2025.116543.
Boris S Dimitrov 1,  Dimpi Mukhopadhyay 1,  Hira Lal Goel 1,  Emmet R Karner 1,  Christi A Silva 1,  Ayush Kumar 1,  Cornelia Peterson 2,  Mengdie Wang 1,  Arthur M Mercurio 3
Affiliations

Affiliations

  • 1 Department of Molecular, Cell and Cancer Biology, University of Massachusetts Chan Medical School, Worcester, MA, USA.
  • 2 Department of Comparative Pathobiology, Tufts University Cummings School of Veterinary Medicine, North Grafton, MA 05136, USA.
  • 3 Department of Molecular, Cell and Cancer Biology, University of Massachusetts Chan Medical School, Worcester, MA, USA. Electronic address: [email protected].
PMID: 41206865 DOI: 10.1016/j.celrep.2025.116543
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 inhibitor reduces metastasis significantly, an effect that is mitigated by a Ferroptosis inhibitor. These results indicate that a sub-population of TNBC cells characterized by TRPC6 expression has the potential to form metastases by evading Ferroptosis.

Keywords

CP: cancer; TRPC6; breast cancer; cancer; ferroptosis; glutathione; metastasis.

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