Background: Increasing evidence indicated that metabolic reprograming is essential and has been regarded as a hallmark of cancer. Although the biological functions of Myosin 1b (Myo1b) have been reported in several malignancies, the correlation between Myo1b and cancer metabolism, and its underlying mechanisms remain elusive, particularly in cervical cancer (CC). Methods: Myo1b and other glycolytic enzymes expression levels were examined in CC cells and tumor tissues from xenograft models by quantitative real-time PCR, Western blot and immunohistochemistry. The biological impacts and regulatory mechanisms of Myo1b on cell migration, invasion and glycolysis were explored. Also, the effects of Myo1b on carcinogenesis and metastasis in nude mice were investigated. Results: Upregulation of Myo1b was found in CC tissues and associated with poor prognosis. Overexpressed Myo1b not only significantly elevated CC cell glycolysis, migration and invasion in vitro, but also promoted tumorigenesis and metastasis in vivo. Conversely, Myo1b knockdown had opposite consequences. Moreover, our study suggested that Myo1b stimulated ERK/HIF-1α pathway and its downstream glycolysis associated genes to modulate the glycolysis, migration and invasion of CC. Conclusion: These findings provide evidence that Myo1b regulates migration, invasion and glycolysis in CC through ERK/HIF-1α pathway, suggesting a promising remedial target in treatment of CC.
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机译：背景： 越来越多的证据表明，代谢重编程是必不可少的，并被视为癌症的标志。尽管肌球蛋白 1b （Myo1b） 的生物学功能已在多种恶性肿瘤中报道，但 Myo1b 与癌症代谢之间的相关性及其潜在机制仍然难以捉摸，尤其是在宫颈癌 （CC） 中。方法： 通过定量实时 PCR、Western blot 和免疫组化检测异种移植模型 CC 细胞和肿瘤组织中 Myo1b 和其他糖酵解酶的表达水平。探讨了 Myo1b 对细胞迁移、侵袭和糖酵解的生物学影响和调控机制。此外，还研究了 Myo1b 对裸鼠致癌和转移的影响。结果： 在 CC 组织中发现 Myo1b 上调，并与不良预后相关。过表达 Myo1b 不仅在体外显著提高 CC 细胞糖酵解、迁移和侵袭，而且在体内促进肿瘤发生和转移。相反，Myo1b 敲低具有相反的后果。此外，我们的研究表明，Myo1b 刺激 ERK/HIF-1α 通路及其下游糖酵解相关基因调节 CC 的糖酵解、迁移和侵袭。结论：这些发现提供了证据，证明 Myo1b 通过 ERK/HIF-1α 通路调节 CC 中的迁移、侵袭和糖酵解，表明 CC 治疗是一个有前途的补救靶点。
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