Cathepsin V Mediates the Tazarotene-induced Gene 1-induced Reduction in Invasion in Colorectal Cancer Cells
- PDF / 2,438,393 Bytes
- 12 Pages / 595.276 x 790.866 pts Page_size
- 23 Downloads / 163 Views
ORIGINAL PAPER
Cathepsin V Mediates the Tazarotene-induced Gene 1-induced Reduction in Invasion in Colorectal Cancer Cells Chun-Hua Wang1,2 Lu-Kai Wang3 Chang-Chieh Wu4 Mao-Liang Chen5 Chan-Yen Kuo5 Rong-Yaun Shyu6 Fu-Ming Tsai 5 ●
●
●
●
●
●
1234567890();,:
1234567890();,:
Received: 28 May 2020 / Accepted: 28 August 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
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. Keywords Tazarotene-induced gene 1 Cathepsin V Urokinase-type plasminogen activator Epithelial–mesenchymal transition Cell invasion ●
●
●
●
Introduction Tazarotene-induced gene 1 (TIG1), also named retinoic acid receptor responder 1 (RARRES1), is a retinoic acid-regulated gene associated with cell differentiation [1, 2], metabolism [3, 4], and cell apoptosis or autophagy [5, 6], and is currently considered one of the most commonly methylated genes involved in the development of multiple cancers [5, 7–10].
Supplementary information The online version of this article (https:// doi.org/10.1007/s12013-020-00940-3) contains supplementary material, which is available to authorized users.
The TIG1 gene encodes a 228-amino-acid protein with a molecular weight of 25.8 kDa [6]. TIG1 is considered to be a transmembrane protein, and its structure is similar to that of the latexin protein [11]. The molecular mechanism underlying tumor suppression driven by TIG1 has been dissected. Ectopic TIG1 expression leads to the repression of mitogenactivated protein kinase [5] and activation of autophagyrelated genes in prostate and cervical cancer cells [5, 6]. Elevated TIG1 expression upregulates G-protein-coupled receptor kinase 5 (GRK5) expression, and GRK5 is involved in the TIG1-regulating Wnt signaling pathway in colorectal cancer cells [12, 13]. The cytoplasmic
* Rong-Yaun Shyu [email protected]
4
* Fu-Ming Tsai [email protected]
Department of Surgery, Tri-Service General Hospital Keelung Branch, National Defense Medical Center, Keelung 202, Taiwan
5
Department of Research, Taipei Tzuchi Hospital, Th
Data Loading...
