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Target: RPL17


Research on RPL17

1. Target Summary:

RPL17 (Ribosomal Protein L17) is a component of the 60S ribosomal subunit involved in protein synthesis. It has been implicated in various cancers, particularly colorectal cancer (CRC), where it promotes cell proliferation and stemness. RPL17 is also associated with other malignancies, including bladder and liver cancers, and serves as a potential prognostic marker.

2. Mechanism:

RPL17 functions primarily as a structural component of the ribosome, facilitating the translation of mRNA into proteins. However, recent studies have revealed that RPL17 may also have extra-ribosomal functions that contribute to oncogenesis.
In colorectal cancer, RPL17 is up-regulated and promotes cancer cell proliferation and stemness through the ERK and NEK2/beta-catenin signaling pathways. Specifically, silencing RPL17 expression leads to decreased levels of NEK2, beta-catenin, and phosphorylated ERK (p-ERK), which are critical for cell cycle progression and maintenance of stem cell characteristics. This results in reduced cell growth, colony formation, and tumor formation in vivo (Ko MJ, Seo YR, Seo D, 2022, PMID: 35711835).
Additionally, RPL17 has been shown to be overexpressed in breast cancer brain metastases, indicating its role in metastasis (Yuan F, Wang W, Cheng H, 2018, PMID: 30546434). The protein's involvement in various signaling pathways suggests that it may influence multiple aspects of cancer biology, including cell migration and invasion.

3. Approved Drugs:

Currently, there are no specific drugs approved that target RPL17 directly. However, therapies that inhibit the pathways associated with RPL17, such as ERK inhibitors, may indirectly affect its function in cancer.

4. Hypotheses:

  1. Oncogenic Role: RPL17 may play a critical role in the progression of multiple cancer types, not just colorectal cancer, due to its involvement in key signaling pathways.
  2. Therapeutic Target: Targeting RPL17 could provide a novel therapeutic strategy for treating cancers where it is up-regulated, potentially leading to reduced tumor growth and improved patient outcomes.
  3. Biomarker Potential: RPL17 expression levels may correlate with cancer prognosis, making it a potential biomarker for early detection and monitoring of treatment efficacy.

5. Validation:

The role of RPL17 in cancer has been validated through various studies:
  • In colorectal cancer, RPL17 silencing resulted in significant reductions in cell growth and tumor formation, confirming its oncogenic role (Ko MJ, Seo YR, Seo D, 2022, PMID: 35711835).
  • Overexpression of RPL17 has been linked to poor prognosis in bladder cancer, where it was found to be significantly higher in cancer tissues compared to normal controls (Liu Z, Zhu F, Zhang P, 2022, PMID: 36506302).
  • The expression of RPL17 has been associated with the presence of perineural invasion in gastric cancer, further supporting its role in tumor progression (Choi ES, Lee H, Lee CH, 2016, PMID: 27833855).

6. Clinical Trials:

As of now, there are no specific clinical trials targeting RPL17 directly. However, ongoing research into the pathways associated with RPL17 may lead to future trials exploring its potential as a therapeutic target.

7. Involved Pathways:

  • ERK Signaling Pathway: RPL17 promotes cell proliferation and stemness through the ERK signaling pathway.
  • NEK2/beta-catenin Pathway: RPL17 influences the NEK2/beta-catenin signaling axis, which is crucial for mitotic progression and stemness maintenance.

8. Associated Genes:

  • NEK2: Down-regulated upon RPL17 silencing, indicating its role in cell cycle regulation.
  • Beta-catenin: A key player in the Wnt signaling pathway, involved in cell proliferation and differentiation.

9. Target Expression:

RPL17 is overexpressed in various cancers, including colorectal, bladder, and breast cancers. Its expression levels correlate with tumor aggressiveness and patient prognosis.

10. Additional Context:

RPL17's role extends beyond ribosomal function, suggesting that ribosomal proteins may have significant implications in cancer biology. Understanding the extra-ribosomal functions of RPL17 could open new avenues for cancer therapy and diagnostics.

11. References:

  • Ko MJ, Seo YR, Seo D. RPL17 Promotes Colorectal Cancer Proliferation and Stemness through ERK and NEK2/beta-catenin Signaling Pathways. Journal of Cancer. 2022. PMID: 35711835.
  • Yuan F, Wang W, Cheng H. Co-expression network analysis of gene expression profiles of HER2(+) breast cancer-associated brain metastasis. Oncology Letters. 2018. PMID: 30546434.
  • Liu Z, Zhu F, Zhang P. Construction of cuproptosis-related gene signature to predict the prognosis and immunotherapy efficacy of patients with bladder cancer through bioinformatics analysis and experimental validation. Frontiers in Genetics. 2022. PMID: 36506302.
  • Choi ES, Lee H, Lee CH. Overexpression of KLHL23 protein from read-through transcription of PHOSPHO2-KLHL23 in gastric cancer increases cell proliferation. FEBS Open Bio. 2016. PMID: 27833855.