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학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2020.1
- 수록면
- 236 - 250 (15page)
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Currently, many available anti-cancer therapies are targeting apoptosis. However, many cancer cells have acquired resistance to apoptosis. To overcome this problem, simultaneous induction of other types of programmed cell death in addition to apoptosis of cancer cells might be an attractive strategy. For this purpose, we initially investigated the inhibitory role of TRIP-Br1/XIAP in necroptosis, a regulated form of necrosis, under nutrient/serum starvation. Our data showed that necroptosis was significantly induced in all tested 9 different types of cancer cell lines in response to prolonged serum starvation. Among them, necroptosis was induced at a relatively lower level in MCF-7 breast cancer line that was highly resistant to apoptosis than that in other cancer cell lines. Interestingly, TRIP-Br1 oncogenic protein level was found to be very high in this cell line. Upregulated TRIP-Br1 suppressed necroptosis by repressing reactive oxygen species generation. Such suppression of necroptosis was greatly enhanced by XIAP, a potent inhibitor of apoptosis. Our data also showed that TRIP-Br1 increased XIAP phosphorylation at serine87, an active form of XIAP. Our mitochondrial fractionation data revealed that TRIPBr1 protein level was greatly increased in the mitochondria upon serum starvation. It suppressed the export of CypD, a vital regulator in mitochondria-mediated necroptosis, from mitochondria to cytosol. TRIP-Br1 also suppressed shikoninmediated necroptosis, but not TNF-α-mediated necroptosis, implying possible presence of another signaling pathway in necroptosis. Taken together, our results suggest that TRIPBr1/XIAP can function as onco-proteins by suppressing necroptosis of cancer cells under nutrient/serum starvation.
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참고문헌 (68)
참고문헌 신청
Aharoni-Simon, M. / 2016 / Bcl-2 regulates reactive oxygen species signaling and a redox-sensitive mitochondrial proton leak in mouse pancreatic β-cells / Endocrinology 157:2270~2281
Belizário, J. / 2015 / Necroptotic cell death signaling and execution pathway : lessons from knockout mice / Mediators Inflamm 2015:128076
Berezovskaya, O. / 2005 / Increased expression of apoptosis inhibitor protein XIAP contributes to anoikis resistance of circulating human prostate cancer metastasis precursor cells increased expression of apoptosis inhibitor protein XIAPcontributes to anoikis resistance of circul / Cancer Res 65:2378~2386
Berghe, T. / 2014 / Regulated necrosis : the expanding network of non-apoptotic cell death pathways / Nat. Rev. Mol. Cell Biol 15:135~147
Bernardi, P. / 2006 / The mitochondrial permeability transition from in vitro artifact to disease target / FEBS J 273:2077~2099
Belizário, J. / 2015 / Necroptotic cell death signaling and execution pathway : lessons from knockout mice / Mediators Inflamm 2015:128076
Berezovskaya, O. / 2005 / Increased expression of apoptosis inhibitor protein XIAP contributes to anoikis resistance of circulating human prostate cancer metastasis precursor cells increased expression of apoptosis inhibitor protein XIAPcontributes to anoikis resistance of circul / Cancer Res 65:2378~2386
Berghe, T. / 2014 / Regulated necrosis : the expanding network of non-apoptotic cell death pathways / Nat. Rev. Mol. Cell Biol 15:135~147
Bernardi, P. / 2006 / The mitochondrial permeability transition from in vitro artifact to disease target / FEBS J 273:2077~2099
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