Xie Lang, Huang Hongyun, Zheng Zheng, Yang Qian, Wang Shubo, Chen Yaoxu, Yu Jinlong, Cui Chunhui
Department of General Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
The Medical Department, 3D Medicines Inc., Shanghai, China.
Ann Transl Med. 2021 Oct;9(20):1543. doi: 10.21037/atm-21-4702.
Colorectal cancer (CRC) has a high worldwide incidence and mortality. Tumor metastasis is one of the primary reasons for the poor prognosis of CRC patients. However, the mechanism underlying CRC metastasis is still unclear. Myosin 1B (MYO1B) is important for cell migration and motility and is part of the myosin superfamily that contains various myosins. Studies of prostate, cervical, and head and neck cancer have revealed preliminary findings concerning the effect of MYO1B on tumor metastasis. However, the role of MYO1B in CRC metastasis, as well as its underlying mechanism, remains unknown.
Quantitative real-time PCR and immunohistochemical staining methods were used to analyze the expression of MYO1B in human CRC and normal mucosa tissues. Lentivirus vector-based MYO1B oligonucleotides and short hairpin RNA (shRNA) were used to examine the functional relevance of MYO1B in CRC cells. Co-immunoprecipitation, western blotting, and immunofluorescence assays were used to investigate the underlying mechanism of MYO1B-mediated cell migration.
The expression of MYO1B was increased in most CRC tissues and was positively associated with a greater risk of tumor metastasis and poor prognosis for patients. MYO1B was significantly associated with the migration and invasion properties of CRC cells and . MYO1B promoted F-actin rearrangement through the ROCK2/LIMK/Cofilin axis by enhancing the activation of RhoA. MYO1B also promoted the assembly of focal adhesions by targeting RhoA.
MYO1B plays a vital role in CRC metastasis by promoting the activation of RhoA. MYO1B may not only be a valid biomarker for predicting the risk of metastasis and poor prognosis in CRC but may also be a potential therapeutic target for patients with a high risk of tumor metastasis.
结直肠癌（CRC）在全球范围内具有较高的发病率和死亡率。肿瘤转移是CRC患者预后不良的主要原因之一。然而，CRC转移的潜在机制仍不清楚。肌球蛋白1B（MYO1B）对细胞迁移和运动很重要，是包含各种肌球蛋白的肌球蛋白超家族的一部分。对前列腺癌、宫颈癌以及头颈癌的研究已经揭示了关于MYO1B对肿瘤转移影响的初步发现。然而，MYO1B在CRC转移中的作用及其潜在机制仍然未知。
采用定量实时PCR和免疫组织化学染色方法分析MYO1B在人CRC组织和正常黏膜组织中的表达。基于慢病毒载体的MYO1B寡核苷酸和短发夹RNA（shRNA）用于检测MYO1B在CRC细胞中的功能相关性。采用免疫共沉淀、蛋白质免疫印迹和免疫荧光分析来研究MYO1B介导细胞迁移的潜在机制。
MYO1B在大多数CRC组织中的表达增加，并且与患者肿瘤转移风险增加和预后不良呈正相关。MYO1B与CRC细胞的迁移和侵袭特性显著相关。MYO1B通过增强RhoA的激活，经由ROCK2/LIMK/丝切蛋白轴促进F-肌动蛋白重排。MYO1B还通过靶向RhoA促进粘着斑的组装。
MYO1B通过促进RhoA的激活在CRC转移中起关键作用。MYO1B不仅可能是预测CRC转移风险和预后不良的有效生物标志物，还可能是肿瘤转移高危患者潜在的治疗靶点。
