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Targeting Bmi1 to Enhance Anoikis and Inhibit CRC Metastasis

August, 08, 2024 | Colorectal Cancer, Gastrointestinal Cancer

KEY TAKEAWAYS

  • The study aimed to investigate the role of Bmi1 in CRC anoikis resistance and metastasis.
  • The results showed that targeting Bmi1 could be a potential therapeutic strategy for advanced CRC treatment.

Metastatic colorectal cancer (CRC) presents a significant challenge with low survival rates. Anoikis resistance, the ability of metastatic cancer cells to evade programmed cell death when detached from the extracellular matrix, plays a crucial role in CRC progression.

Yin-Chou Hsu and the team aimed to investigate the role of the B cell-specific Moloney murine leukemia virus insertion site 1 (Bmi1)-midkine (MDK) axis in anoikis resistance in CRC and how it influences metastasis.

Researchers used bulk flow cytometry and RT-qPCR assays, conducted in vivo experiments with mice and zebrafish, and analyzed patient tissues to study the effects of the Bmi1-MDK axis on cellular responses to anoikis. Bmi1, crucial in tumorigenesis, was investigated for its role in anoikis resistance in CRC and its downstream targets related to metastasis.

The results showed that elevated Bmi1 expression was linked to distant metastasis in CRC. Suppressing Bmi1 significantly reduced the metastatic potential of CRC cells and increased the proportion of apoptotic SW620 cells detached from the matrix. This effect was further amplified by irinotecan, a topoisomerase I inhibitor.

Bmi1 was also found to work with MDK in regulating CRC cell viability, with consistent expression patterns observed in both in vivo models and clinical tissue samples. In summary, Bmi1 regulated CRC metastasis by promoting anoikis resistance and collaborated with MDK to enhance invasion and distant metastasis.

The study’s findings indicate that Bmi1 plays a critical role in promoting anoikis resistance and metastasis in CRC.Targeting Bmi1, potentially in combination with traditional chemotherapy, may be a promising therapeutic approach for managing advanced CRC.

No funding information was given.

Source: https://pubmed.ncbi.nlm.nih.gov/39191496/

Hsu YC, Luo CW, Chang SJ, et al. (2024). “Targeting Bmi1 for Enhancing Anoikis Sensitivity and Inhibiting Metastasis in Colorectal Cancer.” Cancer Genomics Proteomics. 2024;21(5):523-532. doi:10.21873/cgp.20469

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