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Cathepsin V Mediates the Tazarotene-induced Gene 1-induced Reduction in Invasion in Colorectal Cancer Cells

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Abstract

Tazarotene-induced gene 1 (TIG1) is a retinoid acid receptor-responsive gene involved in cell differentiation and tumorigenesis. Aberrant methylation of CpG islands in the TIG1 promoter is found in multiple cancers. Currently, the exact mechanism underlying the anticancer effect of TIG1 is unknown. Here, we show that TIG1 interacts with cathepsin V (CTSV), which reduces CTSV stability and subsequently affects the production of activated urokinase-type plasminogen activator (uPA), an epithelial–mesenchymal transition-associated protein. Ectopic expression of CTSV increased the expression of activated uPA and the number of migrated and invaded cells, whereas ectopic TIG1 expression reversed the effects of CTSV on the uPA signaling pathway. Similar patterns in the production of activated uPA and number of migrated and invaded cells were also observed in TIG1-expressing and CTSV-knockdown cells. The results suggest that CTSV may participate in TIG1-regulated uPA activity and the associated downstream signaling pathway.

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Acknowledgements

This work was supported by grants (TCRD-TPE-108-59 and TCRD-TPE-107-45) from the Taipei Tzuchi Hospital, Taipei, Taiwan, Republic of China. The authors thank the Core Laboratory of the Taipei Tzuchi Hospital for support.

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Authors and Affiliations

  1. Department of Dermatology, Taipei Tzuchi Hospital, Buddhist Tzuchi Medical Foundation, New Taipei City, 231, Taiwan

    Chun-Hua Wang

  2. School of Medicine, Tzu Chi University, Hualien, 970, Taiwan

    Chun-Hua Wang

  3. Radiation Biology Core Laboratory, Institute for Radiological Research, Chang Gung University/Chang Gung Memorial Hospital, Linkou, Taoyuan, 333, Taiwan

    Lu-Kai Wang

  4. Department of Surgery, Tri-Service General Hospital Keelung Branch, National Defense Medical Center, Keelung, 202, Taiwan

    Chang-Chieh Wu

  5. Department of Research, Taipei Tzuchi Hospital, The Buddhist Tzuchi Medical Foundation, New Taipei City, 231, Taiwan

    Mao-Liang Chen, Chan-Yen Kuo & Fu-Ming Tsai

  6. Department of Internal Medicine, Taipei Tzuchi Hospital, The Buddhist Tzuchi Medical Foundation, New Taipei City, 231, Taiwan

    Rong-Yaun Shyu

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  1. Chun-Hua Wang
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Wang, CH., Wang, LK., Wu, CC. et al. Cathepsin V Mediates the Tazarotene-induced Gene 1-induced Reduction in Invasion in Colorectal Cancer Cells. Cell Biochem Biophys 78, 483–494 (2020). https://doi.org/10.1007/s12013-020-00940-3

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