J Cancer 2020; 11(13):3803-3815. doi:10.7150/jca.43826

Research Paper

Integrin αvβ8 serves as a Novel Marker of Poor Prognosis in Colon Carcinoma and Regulates Cell Invasiveness through the Activation of TGF-β1

Mingliang Zhou1,2, Jun Niu3, Jinshen Wang1,2, Huijie Gao3, Muhammad Shahbaz3, Zhengchuan Niu4, Zequn Li5, Xueqing Zou5, Benjia Liang1,2✉

1. Department of Gastrointestinal Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, Shandong, China
2. Department of Gastrointestinal Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, Shandong, China
3. Department of Hepatobiliary Surgery, Qilu Hospital, Shandong University, Jinan 250012 Shandong, China
4. Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai 20032, China
5. Department of Gastrointestinal Surgery, Affiliated Hospital of Qingdao University, Qingdao 266003, Shandong, China

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Citation:
Zhou M, Niu J, Wang J, Gao H, Shahbaz M, Niu Z, Li Z, Zou X, Liang B. Integrin αvβ8 serves as a Novel Marker of Poor Prognosis in Colon Carcinoma and Regulates Cell Invasiveness through the Activation of TGF-β1. J Cancer 2020; 11(13):3803-3815. doi:10.7150/jca.43826. Available from https://www.jcancer.org/v11p3803.htm

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Abstract

Integrin αvβ8 expressed on tumor cells executes crucial regulatory functions during cell adhesion in the tumor microenvironment and supports the activation of TGF-β1. This study aimed to investigate the expression of integrin αvβ8 and its clinical significance in colon cancer, in addition to its influence on the invasion and migration of cancer cells. Our results showed that integrin αvβ8 was an indicator of progression and poor prognosis in patients with colon cancer. Moreover, integrin αvβ8 significantly promoted the invasion and migration of colon cancer cells by the activation of TGF-β1 and upregulation of metalloproteinase-9. Furthermore, suppression of integrin αvβ8 was found to inhibit the growth of colon cancer in vivo. Our results indicate that integrin αvβ8 promotes tumor invasiveness and the migration of colon cancer through TGF-β1 activation and is a potential prognostic biomarker. This study may provide clues to further understand the manner in which the tumor microenvironment mediates the development of colon cancer and develop strategies for novel therapeutic targets in the prevention and treatment of colon cancer.

Keywords: integrin αvβ8, colon cancer, prognostic factors, cell invasiveness, TGF-β1