Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, P.R. China.
The First School of Clinical Medicine, Southern Medical University, Guangzhou, 510515, P.R. China.
Cell Death Dis. 2022 Nov 8;13(11):939. doi: 10.1038/s41419-022-05397-1.
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.
肌球蛋白 1b(Myo1b)是一种重要的单头膜结合肌球蛋白 I 类分子,参与许多关键的生理和病理过程。越来越多的证据表明,Myo1b 表达的失调在几种肿瘤的发生和发展中得到了广泛研究。然而,Myo1b 在 CRC 血管生成和自噬进展中的功能机制尚不清楚。在此,我们发现 Myo1b 在 CRC 组织中表达上调,其高表达与较差的生存相关。Myo1b 的过表达促进了 CRC 细胞的增殖、迁移和侵袭。相反,Myo1b 的沉默抑制了体外和体内的肿瘤进展。进一步的研究表明,Myo1b 抑制了 CRC 细胞自噬体-溶酶体融合,并增强了 VEGF 的分泌,从而促进血管生成。机制上,Myo1b 阻断了 HIF-1α 的自噬降解,导致 HIF-1α 积累,从而增强了 VEGF 的分泌,进而促进了 CRC 中的肿瘤血管生成。总之,我们的研究为 Myo1b 在 CRC 进展中的作用提供了新的见解,并表明它可能是 CRC 患者可行的预测生物标志物和有前途的治疗靶点。