Aging, cancer, and longevity have been linked to intracellular Ca²⁺ signaling and nociceptive transient receptor potential (TRP) channels. We found that TRP canonical 7 (TRPC7) is a nociceptive mechanoreceptor and that TRPC7 channels specifically mediate the initiation of ultraviolet B (UVB)‐induced skin aging and tumor development due to p53 gene family mutations. Within 30 min after UVB irradiation, TRPC7 mediated UVB‐induced Ca²⁺ influx and the subsequent production of reactive oxygen species in skin cells. Notably, this function was unique to TRPC7 and was not observed for other TRP channels. In TRPC7 knockout mice, we did not observe the significant UVB‐associated pathology seen in wild‐type mice, including epidermal thickening, abnormal keratinocyte differentiation, and DNA damage response activation. TRPC7 knockout mice also had significantly fewer UVB‐induced cancerous tumors than did wild‐type mice, and UVB‐induced p53 gene family mutations were prevented in TRPC7 knockout mice. These results indicate that TRPC7 activity is pivotal in the initiation of UVB‐induced skin aging and tumorigenesis and that the reduction in TRPC7 activity suppresses the UVB‐induced aging process and tumor development. Our findings support that TRPC7 is a potential tumor initiator gene and that it causes cell aging and genomic instability, followed by a change in the activity of proto‐oncogenes and tumor suppressor genes to promote tumorigenesis.

中文翻译：

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伤害性瞬时受体潜在规范7（TRPC7）介导紫外线B诱导的衰老相关肿瘤发生。

衰老，癌症和长寿与细胞内Ca ²⁺信号传导和伤害性瞬时受体电位（TRP）通道有关。我们发现TRP规范7（TRPC7）是一种伤害性机械感受器，并且由于p53基因家族突变，TRPC7通道特异性介导了紫外线B（UVB）诱导的皮肤衰老和肿瘤发展的启动。UVB照射后30分钟内，TRPC7介导UVB诱导的Ca ^2+内流以及随后在皮肤细胞中产生活性氧。值得注意的是，此功能是TRPC7独有的，其他TRP通道则未观察到。在TRPC7中剔除小鼠，我们没有观察到野生型小鼠中明显的与UVB相关的病理，包括表皮增厚，异常的角质形成细胞分化和DNA损伤反应激活。TRPC7基因敲除小鼠还比野生型小鼠明显少了UVB诱导的癌性肿瘤，并且TRPC7基因敲除的小鼠可以预防UVB诱导的p53基因家族突变。这些结果表明，TRPC7活性在引发UVB诱导的皮肤衰老和肿瘤发生中起着关键作用，而TRPC7活性的降低则抑制了UVB诱导的衰老过程和肿瘤的发展。我们的发现支持TRPC7 是潜在的肿瘤启动子基因，它会引起细胞衰老和基因组不稳定，随后改变原癌基因和抑癌基因的活性以促进肿瘤发生。