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Colon cancer stem cells resist antiangiogenesis therapy-induced apoptosis
Shih-Pei Lin1, Yi-Ting Lee, Shung-Haur Yang
1Institute of Clinical Medicine, Faculty of Medicine, National Yang-Ming University, Taipei 112, Taiwan.
Abstract:
Antiangiogenesis is an efficient therapy for eliminating colon cancers, but because of recurrence it remains only palliative. We hypothesized that certain populations of tumor cells resist antiangiogenesis-induced apoptosis and explored the underlying mechanism. We demonstrated that the CD133(+) population of cells in colon cancer is resistant to anti-angiogenesis therapy. Additionally, we identified an anti-apoptotic signaling pathway responsible for this resistance involving PP2A, p38MAPK, MAPKAPK2, and Hsp27. Thus, this pathway may offer a new avenue to develop target therapy for colorectal cancer.
Insights
Certain colon cancer cells resist anti-angiogenesis therapy due to a specific signaling pathway. Targeting this pathway involving PP2A, p38MAPK, MAPKAPK2, and Hsp27 may improve colorectal cancer treatment.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Antiangiogenesis therapy is effective for colon cancer but often palliative due to recurrence.
- Tumor cell resistance to antiangiogenesis limits treatment efficacy.
- Understanding resistance mechanisms is crucial for improving colorectal cancer therapies.
Purpose of the Study:
- To investigate the mechanism of tumor cell resistance to antiangiogenesis therapy in colon cancer.
- To identify specific cancer cell populations that resist antiangiogenesis.
- To elucidate the molecular pathways involved in this resistance.
Main Methods:
- Analysis of CD133(+) cell populations in colon cancer.
- Investigation of apoptosis resistance mechanisms.
- Identification of key signaling molecules including PP2A, p38MAPK, MAPKAPK2, and Hsp27.
Main Results:
- The CD133(+) cell population in colon cancer exhibits resistance to anti-angiogenesis therapy.
- An anti-apoptotic signaling pathway involving PP2A, p38MAPK, MAPKAPK2, and Hsp27 was identified as responsible for this resistance.
- This pathway confers resistance to antiangiogenesis-induced apoptosis.
Conclusions:
- CD133(+) cells are a resistant population in antiangiogenesis therapy for colon cancer.
- The identified signaling pathway presents a potential therapeutic target for overcoming resistance.
- Targeting this pathway could lead to more effective treatments for colorectal cancer.
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