Myo1b promotes tumor progression and angiogenesis by inhibiting autophagic degradation of HIF-1α in colorectal cancer.
Myo1b promotes tumor progression and angiogenesis by inhibiting autophagic degradation of HIF-1α in colorectal cancer.
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DOI：
10.1038/s41419-022-05397-1
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发表时间：
2022-11-08
影响因子：
9
通讯作者：
Zhou, Jue-Yu
中科院分区：
文献类型：
--
作者：
Chen, Yi-Hong;Xu, Nan-Zhu;Hong, Chang;Li, Wen-Qi;Zhang, Yi-Qiong;Yu, Xin-Yi;Huang, Yue-Le;Zhou, Jue-Yu
肌球蛋白1b（Myosin 1b，Myo 1b）是一类重要的单头肌球蛋白马达，参与许多重要的生理和病理过程。越来越多的证据表明，Myo 1b表达的失调已被广泛研究的发展和进展的几种肿瘤。然而，Myo 1b在CRC血管生成和自噬进展中的功能机制仍不清楚。在此，我们发现Myo 1b在结直肠癌组织中表达上调，其高表达与较差的生存相关。Myo 1b的过表达促进了大肠癌细胞的增殖、迁移和侵袭。相反，Myo 1b的沉默抑制了体外和体内的肿瘤进展。进一步的研究表明Myo 1b可抑制自噬体-溶酶体融合，并增强大肠癌细胞VEGF的分泌，促进肿瘤血管生成。Myo 1b通过阻断HIF-1α的自噬降解，导致HIF-1α的聚集，从而促进VEGF的分泌，进而促进肿瘤血管生成。总之，我们的研究为Myo 1b在CRC进展中的作用提供了新的见解，并揭示了它可能是CRC患者可行的预测生物标志物和有前途的治疗靶点。
Myosin 1b (Myo1b) is an important single-headed membrane-associated motor of class I myosins that participate in many critical physiological and pathological processes. Mounting evidence suggests that the dysregulation of Myo1b expression has been extensively investigated in the development and progression of several tumors. However, the functional mechanism of Myo1b in CRC angiogenesis and autophagy progression remains unclear. Herein, we found that the expression of Myo1b was upregulated in CRC tissues and its high expression was correlated with worse survival. The overexpression of Myo1b promoted the proliferation, migration and invasion of CRC cells. Conversely, silencing of Myo1b suppressed tumor progression both in vitro and in vivo. Further studies indicated that Myo1b inhibited the autophagosome-lysosome fusion and potentiated the VEGF secretion of CRC cells to promote angiogenesis. Mechanistically, Myo1b blocked the autophagic degradation of HIF-1α and then led to the accumulation of HIF-1α, thus enhancing VEGF secretion and then promoting tumor angiogenesis in CRC. Together, our study provided novel insights into the role of Myo1b in CRC progression and revealed that it might be a feasible predictive biomarker and promising therapeutic target for CRC patients.
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影响因子：
3.8
作者：
Chapman BV;Wald AI;Akhtar P;Munko AC;Xu J;Gibson SP;Grandis JR;Ferris RL;Khan SA
通讯作者：
Khan SA
环状RNA circ-ERBIN通过miR-125a-5p和miR-138-5p/4EBP-1介导的不依赖帽的HIF-1 α翻译促进结直肠癌的生长和转移
影响因子：
37.3
作者：
Chen LY;Wang L;Ren YX;Pang Z;Liu Y;Sun XD;Tu J;Zhi Z;Qin Y;Sun LN;Li JM
通讯作者：
Li JM
DOI：
10.1073/pnas.1108411109
发表时间：
2012-01-31
影响因子：
11.1
作者：
Mazzolini, Rocco;Dopeso, Higinio;Arango, Diego
通讯作者：
Arango, Diego
4-羟基汉黄芩素通过破坏 PI3K/AKT 信号传导抑制结直肠癌血管生成
影响因子：
5.1
作者：
Sun, Dongdong;Zhang, Feng;Cheng, Haibo
通讯作者：
Cheng, Haibo
DOI：
10.1186/s13046-018-0975-0
发表时间：
2018-12-12
影响因子：
11.3
作者：
Ciccone, Valerio;Terzuoli, Erika;Ziche, Marina
通讯作者：
Ziche, Marina