CTSG Suppresses Colorectal Cancer Progression through Negative Regulation of Akt/mTOR/Bcl2 Signaling Pathway

Chan, Shixin; Wang, Xu; Wang, Zhenglin; Du, Youwen; Zuo, Xiaomin; Chen, Jiajie; Sun, Rui; Zhang, Qing; Lin, Li; Yang, Yang; Yu, Zhen; Zhao, Hu; Zhang, Huabing; Chen, Wei

doi:10.7150/ijbs.82000

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Theranostics

International Journal of Medical Sciences

Nanotheranostics

Journal of Cancer

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Int J Biol Sci 2023; 19(7):2220-2233. doi:10.7150/ijbs.82000 This issue Cite

Research Paper

CTSG Suppresses Colorectal Cancer Progression through Negative Regulation of Akt/mTOR/Bcl2 Signaling Pathway

Shixin Chan^1*, Xu Wang^1*, Zhenglin Wang^1*, Youwen Du⁴, Xiaomin Zuo¹, Jiajie Chen⁵, Rui Sun¹, Qing Zhang², Li Lin², Yang Yang¹, Zhen Yu¹, Hu Zhao¹, Huabing Zhang^2,3✉, Wei Chen^1,6✉

1. Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei 230032, Anhui, China.
2. Department of Biochemistry and Molecular Biology, Metabolic Disease Research Center, School of Basic Medicine, Anhui Medical University, Hefei 230032, Anhui, China.
3. Affiliated Chuzhou Hospital of Anhui Medical University, First People's Hospital of Chuzhou, Chuzhou 239000, Anhui, China.
4. School of Life Sciences, Anhui Medical University, Hefei 230022, Anhui, China.
5. Department of Dermatology, First Affiliated Hospital of Anhui Medical University, Hefei 230022, Anhui, China.
6. Anhui Provincial Institute of Translational Medicine, Hefei 230022, Anhui, China.
* These authors have contributed equally.

Citation:

Chan S, Wang X, Wang Z, Du Y, Zuo X, Chen J, Sun R, Zhang Q, Lin L, Yang Y, Yu Z, Zhao H, Zhang H, Chen W. CTSG Suppresses Colorectal Cancer Progression through Negative Regulation of Akt/mTOR/Bcl2 Signaling Pathway. Int J Biol Sci 2023; 19(7):2220-2233. doi:10.7150/ijbs.82000. https://www.ijbs.com/v19p2220.htm

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Abstract

Colorectal cancer (CRC) is the most common gastrointestinal tumor worldwide, which is a severe malignant disease that threatens mankind. Cathepsin G (CTSG) has been reported to be associated with tumorigenesis, whereas its role in CRC is still unclear. This investigation aims to determine the function of CTSG in CRC. Our results indicated that CTSG was inhibited in CRC tissues, and patients with CTSG low expression have poor overall survival. Functional experiments revealed that CTSG overexpression suppressed CRC cell progression in vitro and in vivo, whereas CTSG suppression supports CRC development cells in vitro and in vivo. Mechanistically, CTSG overexpression suppressed Akt/mTOR signaling mechanism and elevated apoptotic-associated markers, and CTSG silencing activated Akt/mTOR signaling mechanisms and inhibited apoptotic-associated markers. Furthermore, the Akt suppression signaling pathway by MK2206 abolishes CTSG-silenced expression-induced cell viability and Bcl2 up-regulation in vitro and in vivo. Altogether, these outcomes demonstrate that CTSG may act as a tumor suppressor gene via Akt/mTOR/Bcl2-mediated anti-apoptotic signaling inactivation, and CTSG represents a potential therapeutic target in CRC.

Keywords: CTSG, colorectal cancer, Akt, mTOR, Bcl2

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APA

Chan, S., Wang, X., Wang, Z., Du, Y., Zuo, X., Chen, J., Sun, R., Zhang, Q., Lin, L., Yang, Y., Yu, Z., Zhao, H., Zhang, H., Chen, W. (2023). CTSG Suppresses Colorectal Cancer Progression through Negative Regulation of Akt/mTOR/Bcl2 Signaling Pathway. International Journal of Biological Sciences, 19(7), 2220-2233. https://doi.org/10.7150/ijbs.82000.

ACS

Chan, S.; Wang, X.; Wang, Z.; Du, Y.; Zuo, X.; Chen, J.; Sun, R.; Zhang, Q.; Lin, L.; Yang, Y.; Yu, Z.; Zhao, H.; Zhang, H.; Chen, W. CTSG Suppresses Colorectal Cancer Progression through Negative Regulation of Akt/mTOR/Bcl2 Signaling Pathway. Int. J. Biol. Sci. 2023, 19 (7), 2220-2233. DOI: 10.7150/ijbs.82000.

NLM

CSE

Chan S, Wang X, Wang Z, Du Y, Zuo X, Chen J, Sun R, Zhang Q, Lin L, Yang Y, Yu Z, Zhao H, Zhang H, Chen W. 2023. CTSG Suppresses Colorectal Cancer Progression through Negative Regulation of Akt/mTOR/Bcl2 Signaling Pathway. Int J Biol Sci. 19(7):2220-2233.

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