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Protein-protein interaction analysis reveals a novel cancer stem cell related target TMEM17 in colorectal cancer
Zhao-Liang Yu1,2, Yu-Feng Chen1,2, Bin Zheng2,3
1Department of Colorectal Surgery, The Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China.
Background:
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.
Methods:
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.
Results:
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.
Conclusion:
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).
Insights
Targeting TMEM17 may overcome chemoresistance and recurrence in colorectal cancer (CRC). This study identifies TMEM17 as a novel therapeutic target by analyzing cancer stem cells (CSCs) and their associated proteins.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Stem Cell Research
Background:
- Cancer stem cells (CSCs) drive chemoresistance and recurrence in colorectal cancer (CRC).
- A significant unmet need exists for reliable therapeutic targets against CSCs in CRC.
Purpose of the Study:
- To identify and validate novel therapeutic targets for colorectal cancer (CRC) stem cells.
- To investigate the role of TMEM17 protein in CRC progression and chemoresistance.
Main Methods:
- Utilized protein-protein interaction (PPI) databases and gene expression profiles for network analysis.
- Identified and validated TMEM17 as a colon CSC-related gene.
- Performed in-vitro functional studies and Gene Set Enrichment Analysis (GSEA) to examine TMEM17's role and mechanisms in CRC.
Main Results:
- TMEM17 was identified as a novel gene associated with colon CSCs.
- TMEM17 depletion inhibited CRC cell proliferation and enhanced chemosensitivity.
- TMEM17 expression correlates with Wnt/β-catenin pathway activation and is linked to poor patient survival in CRC.
Conclusions:
- TMEM17 plays a critical role in colorectal cancer (CRC) progression.
- TMEM17 represents a potential therapeutic target to address tumor recurrence and chemoresistance in CRC.
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