Protein–protein interaction analysis reveals a novel cancer stem cell related target TMEM17 in colorectal cancer

Cancer Cell International

Jia Ke¹  Yu-feng Chen¹  Zhao-liang Yu¹  Yi-feng Zou¹  Ze-rong Cai¹  Ping Lan²  Xiao-jian Wu²  Bin Zheng³  Feng Gao³ 

[1] Department of Colorectal Surgery, The Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China;Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital of Sun Yat-Sen University, 26 Yuancun Erheng Rd, 510655, Guangzhou, Guangdong, China;Department of Colorectal Surgery, The Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China;Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital of Sun Yat-Sen University, 26 Yuancun Erheng Rd, 510655, Guangzhou, Guangdong, China;Guangdong Institute of Gastroenterology, Guangzhou, China;Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital of Sun Yat-Sen University, 26 Yuancun Erheng Rd, 510655, Guangzhou, Guangdong, China;Guangdong Institute of Gastroenterology, Guangzhou, China;

关键词: Colorectal cancer;    Cancer stem cell;    TMEM17;    Chemoresistance;    Protein–protein interaction;   

DOI  :  10.1186/s12935-021-01794-2

来源: Springer

【 摘 要 】

BackgroundCancer stem cells (CSCs) are a small subpopulation of cells within tumors with stem cell property. Increased evidence suggest that CSCs could be responsible for chemoresistance and recurrence in colorectal cancer (CRC). However, a reliable therapeutic target on CSCs is still lacking.MethodsHere we describe a two-step strategy to generate CSC targets with high selectivity for colon stem cell markers, specific proteins that are interacted with CSC markers were selected and subsequently validated in a survival analysis. TMEM17 protein was found and its biological functions in CRC cells were further examined. Finally, we utilized the Gene Set Enrichment Analysis (GSEA) to investigate the potential mechanisms of TMEM17 in CRC.ResultsBy combining protein–protein interaction (PPI) database and high-throughput gene profiles, network analysis revealed a cluster of colon CSCs related genes. In the cluster, TMEM17 was identified as a novel CSCs related gene. The results of in-vitro functional study demonstrated that TMEM17 depletion can suppress the proliferation of CRC cells and sensitize CRC cells to chemotherapy drugs. Enrichment analysis revealed that the expression of TMEM17 is associated with the magnitude of activation of the Wnt/β-catenin pathway. Further validation in clinical samples demonstrated that the TMEM17 expression was much higher in tumor than normal tissue and was associated with poor survival in CRC patients.ConclusionCollectively, our finding unveils the critical role of TMEM17 in CRC and TMEM17 could be a potential effective therapeutic target for tumor recurrence and chemoresistance in the colorectal cancer (CRC).

【 授权许可】

CC BY