UbcH10 overexpression increases carcinogenesis and blocks ALLN susceptibility in colorectal cancer.
UbcH10 overexpression increases carcinogenesis and blocks ALLN susceptibility in colorectal cancer.
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UbcH10 过表达会增加结直肠癌的致癌作用并阻断 ALLN 的易感性
DOI：
10.1038/srep06910
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发表时间：
2014-11-07
影响因子：
4.6
通讯作者：
Du RL
中科院分区：
文献类型：
--
作者：
Li SZ;Song Y;Zhang HH;Jin BX;Liu Y;Liu WB;Zhang XD;Du RL
细胞周期蛋白是所有真核生物中细胞增殖、细胞周期和肿瘤发生所必需的。UbcH 10以泛素依赖的方式调节细胞周期蛋白的降解。在这里，我们报告UbcH 10可能参与肿瘤发生。我们发现，暴露于N-乙酰基-亮-亮-正亮氨酸（ALLN）治疗和UbcH 10耗竭的癌细胞表现出协同治疗作用。UbcH 10的丰富表达驱动对ALL-诱导的细胞死亡的抗性，而UbcH 10缺陷的细胞对ALL-诱导的细胞死亡敏感。通过集落形成、生长曲线、软琼脂和异种移植试验，证实UbcH 10的缺失抑制了体外和体内的肿瘤发生。通过引入重组UbcH 10，这些表型被有效地拯救。在UbcH 10缺陷细胞中，细胞周期蛋白表达的改变导致细胞周期的变化，随后降低肿瘤发生。在裸鼠中，相对于用ALLN处理的野生型细胞，用ALLN处理的UbcH 10缺陷细胞的异种移植瘤的肿瘤发生减少。在分子水平上，我们观察到UbcH 10缺陷增强了半胱天冬酶8和半胱天冬酶3的活化，但不增强半胱天冬酶9的活化，从而损害ALLN处理后的细胞活力。总的来说，我们的研究结果表明，作为一种癌基因，UbcH 10是一个潜在的药物靶点，用于治疗结直肠癌。
Cyclins are essential for cell proliferation, the cell cycle and tumorigenesis in all eukaryotes. UbcH10 regulates the degradation of cyclins in a ubiquitin-dependent manner. Here, we report that UbcH10 is likely involved in tumorigenesis. We found that cancer cells exposed to n-acetyl-leu-leu-norleucinal (ALLN) treatment and UbcH10 depletion exhibit a synergistic therapeutic effect. Abundant expression of UbcH10 drives resistance to ALLN-induced cell death, while cells deficient in UbcH10 were susceptible to ALLN-induced cell death. The depletion of UbcH10 hindered tumorigenesis bothin vitroandin vivo, as assessed by colony formation, growth curve, soft agar and xenograft assays. These phenotypes were efficiently rescued through the introduction of recombinant UbcH10. In the UbcH10-deficient cells, alterations in the expression of cyclins led to cell cycle changes and subsequently decreases in tumorigenesis. The tumorigenesis of xenograft tumors from UbcH10-deficient cells treated with ALLN was decreased relative to wild-type cells treated with ALLN in nude mice. On the molecular level, we observed that UbcH10 deficiency enhances the activation of caspase 8 and caspase 3 but not caspase 9 to impair cell viability upon ALLN treatment. Collectively, our results suggest that, as an oncogene, UbcH10 is a potential drug target for the treatment of colorectal cancer.
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DOI：
10.1111/j.1440-1681.2009.05348.x
发表时间：
2010-05-01
影响因子：
2.9
作者：
Chen, Shi-Min;Jiang, Chun-Ying;Liu, Xian-Xi
通讯作者：
Liu, Xian-Xi
影响因子：
64.5
作者：
Rape, M;Reddy, SK;Kirschner, MW
通讯作者：
Kirschner, MW
DOI：
10.1073/pnas.93.15.7950
发表时间：
1996-07-23
影响因子：
11.1
作者：
Morin, PJ;Vogelstein, B;Kinzler, KW
通讯作者：
Kinzler, KW
影响因子：
64.8
作者：
GLOTZER, M;MURRAY, AW;KIRSCHNER, MW
通讯作者：
KIRSCHNER, MW
DOI：
10.1158/1940-6207.capr-09-0084
发表时间：
2009-08
期刊：
Cancer prevention research (Philadelphia, Pa.)
影响因子：
--
作者：
Kadara H;Lacroix L;Behrens C;Solis L;Gu X;Lee JJ;Tahara E;Lotan D;Hong WK;Wistuba II;Lotan R
通讯作者：
Lotan R