Nociceptive transient receptor potential canonical 7 (TRPC7) mediates aging-associated tumorigenesis induced by ultraviolet B
Journal
Aging Cell
Journal Volume
19
Journal Issue
1
Pages
Article number e13075
Date Issued
2020
Author(s)
Hsu, W.-L.
Tsai, M.-H.
Wu, C.-Y.
Liang, J.-L.
Lu, J.-H.
Kahle, J.S.
Yu, H.-S.
Yen, C.-J.
Yen, C.-T.
Hsieh, Y.-C.
Huang, Y.-Y.
Lin, L.-C.
Tsai, T.-F.
Chen, C.-H.
Yoshioka, T.
Abstract
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. ? 2019 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd
Subjects
aging; p53; TRPC7; tumor initiator gene; tumorigenesis; ultraviolet pathology
SDGs
Other Subjects
phospholipase C; protein p53; reactive oxygen metabolite; transient receptor potential channel 7; transient receptor potential channel C; TRPC7 protein, human; Trpc7 protein, mouse; analgesia; animal experiment; Article; carcinogenesis; cell differentiation; controlled study; cutaneous parameters; DNA damage response; genomic instability; immunohistochemistry; keratinocyte; mechanoreceptor; mouse; multigene family; nociception; nonhuman; phenotype; priority journal; proto oncogene; skin cell; tumor growth; tumor suppressor gene; ultraviolet B radiation; upregulation; whole exome sequencing; animal; carcinogenesis; cutaneous parameters; genetics; human; knockout mouse; radiation response; ultraviolet radiation; Animals; Carcinogenesis; Humans; Keratinocytes; Mice; Mice, Knockout; Skin Aging; TRPC Cation Channels; Ultraviolet Rays
Publisher
Blackwell Publishing Ltd
Type
journal article