2. Academic Validation
  3. Nociceptive transient receptor potential canonical 7 (TRPC7) mediates aging-associated tumorigenesis induced by ultraviolet B

Nociceptive transient receptor potential canonical 7 (TRPC7) mediates aging-associated tumorigenesis induced by ultraviolet B

  • Aging Cell. 2020 Jan;19(1):e13075. doi: 10.1111/acel.13075.
Wen-Li Hsu 1 2 3,  Ming-Hsien Tsai 2 4,  Ching-Ying Wu 5 6,  Jui-Lin Liang 7,  Jian-He Lu 6,  Jennifer S Kahle 8 9,  Hsin-Su Yu 10,  Chia-Jung Yen 3 4,  Chen-Tung Yen 11,  Yi-Chun Hsieh 2 4,  Yung-Yun Huang 12,  Li-Ching Lin 12,  Tsung-Fu Tsai 12,  Chu-Huang Chen 6 13 14 15 16,  Tohru Yoshioka 3 6
Affiliations

Affiliations

  • 1 Research Organization for Nano & Life Innovation, Waseda University, Shinjuku, Tokyo, Japan.
  • 2 Emerging Compounds Research Center, General Research Service Center, National Pingtung University of Science and Technology, Pingtung, Taiwan.
  • 3 Regenerative Medicine and Cell Therapy Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan.
  • 4 Department of Child Care, College of Humanities and Social Sciences, National Pingtung University of Science and Technology, Pingtung, Taiwan.
  • 5 Department of Dermatology, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
  • 6 Graduate Institute of Medicine, School of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
  • 7 Department of General Surgery, Chi-Mei Medical Center, Liouying, Tainan, Taiwan.
  • 8 Department of Psychological Sciences, University of San Diego, San Diego, CA, USA.
  • 9 BPS, International, San Diego, CA, USA.
  • 10 Department of Dermatology, Kaohsiung Medical University, Kaohsiung, Taiwan.
  • 11 Department of Life Science, National Taiwan University, Taipei, Taiwan.
  • 12 School of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
  • 13 Center for Lipid Biosciences, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
  • 14 Vascular and Medicinal Research, Texas Heart Institute, Houston, TX, USA.
  • 15 New York Heart Research Foundation, Mineola, NY, USA.
  • 16 Lipid Science and Aging Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan.
PMID: 31755176 DOI: 10.1111/acel.13075
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.

Keywords

TRPC7; aging; p53; tumor initiator gene; tumorigenesis; ultraviolet pathology.

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