癌症干细胞（CSC）是具有高致瘤潜力的细胞亚群，导致治疗耐药、转移和复发。根除CSC被广泛认为是改善患者预后的关键因素，但有效靶向这些细胞仍然是一个重大挑战。在这里，我们表明溶酶体阳离子通道 TRPML1 代表了 CSC 的一个有前途的靶点。 TRPML1 在乳腺癌细胞中高度表达，并对盐霉素（一种已知可选择性消除 CSC 的药物）敏感。 TRPML1 的药理学抑制和基因敲除可促进乳腺 CSC 的铁死亡，降低其干性，并增强乳腺癌细胞对化疗药物阿霉素的敏感性。在小鼠异种移植模型中，TRPML1 的抑制和敲除也显示出对肿瘤形成和生长的显着抑制。这些发现表明，靶向 TRPML1 来消除 CSC 可能是治疗乳腺癌的有效策略。© 2024。作者。

Cancer stem cells (CSCs) are a sub-population of cells possessing high tumorigenic potential, which contribute to therapeutic resistance, metastasis and recurrence. Eradication of CSCs is widely recognized as a crucial factor in improving patient prognosis, yet the effective targeting of these cells remains a major challenge. Here, we show that the lysosomal cation channel TRPML1 represents a promising target for CSCs. TRPML1 is highly expressed in breast cancer cells and exhibits sensitivity to salinomycin, a drug known to selectively eliminate CSCs. Pharmacological inhibition and genetic depletion of TRPML1 promote ferroptosis in breast CSCs, reduce their stemness, and enhance the sensitivity of breast cancer cells to chemotherapy drug doxorubicin. The inhibition and knockout of TRPML1 also demonstrate significant suppression of tumor formation and growth in the mouse xenograft model. These findings suggest that targeting TRPML1 to eliminate CSCs may be an effective strategy for the treatment of breast cancer.© 2024. The Author(s).