Int J Biol Sci 2022; 18(13):4932-4949. doi:10.7150/ijbs.76425 This issue Cite

Research Paper

CPNE8 Promotes Gastric Cancer Metastasis by Modulating Focal Adhesion Pathway and Tumor Microenvironment

Peiling Zhang1#, Xiaofei Cao1#, Mingmei Guan1#, Dailing Li1, Hong Xiang1, Qian Peng1, Yun Zhou1, Chengyin Weng1, Xisheng Fang1, Xia Liu1, Haibo Mao1, Qiao Li2✉, Guolong Liu1✉, Lin Lu1 ✉

1. Department of Medical Oncology, the Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong, China
2. Department of Surgery University of Michigan, Ann Arbor, Michigan, USA
# Peiling Zhang, Xiaofei Cao and Mingmei Guan contributed equally to this work

Citation:
Zhang P, Cao X, Guan M, Li D, Xiang H, Peng Q, Zhou Y, Weng C, Fang X, Liu X, Mao H, Li Q, Liu G, Lu L. CPNE8 Promotes Gastric Cancer Metastasis by Modulating Focal Adhesion Pathway and Tumor Microenvironment. Int J Biol Sci 2022; 18(13):4932-4949. doi:10.7150/ijbs.76425. https://www.ijbs.com/v18p4932.htm
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Abstract

Graphic abstract

Little is known about the oncogenic role or biological function of copine Ⅷ (CPNE8) in gastric cancer (GC). Based on TCGA database, we screened for CPNE8 and analyzed the expression of CPNE8 in GC. The correlations between CPNE8 and clinical features were analyzed using TCGA and GEO databases. The prognostic value of CPNE8 was assessed using Cox analysis and Kaplan-Meier curves. The results showed that increased expression of CPNE8 was positively correlated with metastasis and can be considered an independent prognostic risk factor for poor survival. We found that CPNE8 can promote cell proliferation, migration, and invasiveness in GC using in vitro and in vivo experiments. Our study demonstrated that CPNE8 promotes tumor progression via regulation of focal adhesion, and these effects can be rescued by focal adhesion kinase (FAK) inhibitor GSK2256098 or knockdown of FAK. In addition, CPNE8 was correlated significantly with the infiltration of cancer-associated fibroblasts and immune cells, as demonstrated by various algorithms, and high CPNE8 expression predicted poor efficacy of immune checkpoint therapy. Our findings suggest that CPNE8 modulates focal adhesion and tumor microenvironment to promote GC progression and invasiveness and could serve as a novel prognostic biomarker in GC.

Keywords: CPNE8, Gastric cancer, Metastasis, Focal adhesion, Tumor microenvironment.


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APA
Zhang, P., Cao, X., Guan, M., Li, D., Xiang, H., Peng, Q., Zhou, Y., Weng, C., Fang, X., Liu, X., Mao, H., Li, Q., Liu, G., Lu, L. (2022). CPNE8 Promotes Gastric Cancer Metastasis by Modulating Focal Adhesion Pathway and Tumor Microenvironment. International Journal of Biological Sciences, 18(13), 4932-4949. https://doi.org/10.7150/ijbs.76425.

ACS
Zhang, P.; Cao, X.; Guan, M.; Li, D.; Xiang, H.; Peng, Q.; Zhou, Y.; Weng, C.; Fang, X.; Liu, X.; Mao, H.; Li, Q.; Liu, G.; Lu, L. CPNE8 Promotes Gastric Cancer Metastasis by Modulating Focal Adhesion Pathway and Tumor Microenvironment. Int. J. Biol. Sci. 2022, 18 (13), 4932-4949. DOI: 10.7150/ijbs.76425.

NLM
Zhang P, Cao X, Guan M, Li D, Xiang H, Peng Q, Zhou Y, Weng C, Fang X, Liu X, Mao H, Li Q, Liu G, Lu L. CPNE8 Promotes Gastric Cancer Metastasis by Modulating Focal Adhesion Pathway and Tumor Microenvironment. Int J Biol Sci 2022; 18(13):4932-4949. doi:10.7150/ijbs.76425. https://www.ijbs.com/v18p4932.htm

CSE
Zhang P, Cao X, Guan M, Li D, Xiang H, Peng Q, Zhou Y, Weng C, Fang X, Liu X, Mao H, Li Q, Liu G, Lu L. 2022. CPNE8 Promotes Gastric Cancer Metastasis by Modulating Focal Adhesion Pathway and Tumor Microenvironment. Int J Biol Sci. 18(13):4932-4949.

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