Protein-protein interaction analysis reveals a novel cancer stem cell related target TMEM17 in colorectal cancer.
Protein-protein interaction analysis reveals a novel cancer stem cell related target TMEM17 in colorectal cancer.
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DOI:
10.1186/s12935-021-01794-2
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发表时间:
2021-02-06
影响因子:
5.8
通讯作者:
Wu XJ
中科院分区:
文献类型:
--
作者:
Yu ZL;Chen YF;Zheng B;Cai ZR;Zou YF;Ke J;Lan P;Gao F;Wu XJ
Cancer 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. Here 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. By 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. Collectively, 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).
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影响因子:
37.3
作者:
Gasch C;Ffrench B;O'Leary JJ;Gallagher MF
通讯作者:
Gallagher MF
影响因子:
11.2
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Huang EH;Hynes MJ;Zhang T;Ginestier C;Dontu G;Appelman H;Fields JZ;Wicha MS;Boman BM
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16.6
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Li Z;Ivanov AA;Su R;Gonzalez-Pecchi V;Qi Q;Liu S;Webber P;McMillan E;Rusnak L;Pham C;Chen X;Mo X;Revennaugh B;Zhou W;Marcus A;Harati S;Chen X;Johns MA;White MA;Moreno C;Cooper LA;Du Y;Khuri FR;Fu H
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Fu H
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48
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Li T;Wernersson R;Hansen RB;Horn H;Mercer J;Slodkowicz G;Workman CT;Rigina O;Rapacki K;Stærfeldt HH;Brunak S;Jensen TS;Lage K
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Lage K
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3.7
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Lin HX;Qiu HJ;Zeng F;Rao HL;Yang GF;Kung HF;Zhu XF;Zeng YX;Cai MY;Xie D
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Xie D