肌球蛋白 1e 缺乏会影响 4T1 乳腺癌细胞的迁移。

Michael E Garone, Sharon E Chase, Chunling Zhang, Mira Krendel
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摘要

乳腺癌细胞向远处组织转移是造成乳腺癌相关死亡的主要原因。此前,我们利用小鼠乳腺肿瘤病毒-多瘤中间 T 抗原(MMTV-PyMT)小鼠模型研究了 I 类肌球蛋白运动蛋白肌球蛋白 1e(myo1e)在癌症转移中的作用。与野生型小鼠相比,缺失 myo1e 的小鼠形成的肿瘤表型分化程度更高,而且不会形成可检测到的肺转移灶。在目前的研究中,我们利用高侵袭性和高迁移性乳腺癌细胞系 4T1 研究了 myo1e 的缺失如何影响体外细胞迁移和侵袭。与 WT 4T1 细胞相比,缺失 myo1e 的 4T1 细胞在伤口愈合和跨孔迁移试验中表现出形态改变和迁移速度减慢。虽然整合素的贩运和高尔基体的重新定向在myo1e缺失后似乎没有发生改变,但我们观察到myo1e缺失的细胞中局灶粘附的解体率较低,这可能有助于解释细胞迁移缺陷。
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Myosin 1e deficiency affects migration of 4T1 breast cancer cells.

Metastasis of breast cancer cells to distant tissue sites is responsible for the majority of deaths associated with breast cancer. Previously we have examined the role of class I myosin motor protein, myosin 1e (myo1e), in cancer metastasis using the Mouse Mammary Tumor Virus-Polyoma Middle T Antigen (MMTV-PyMT) mouse model. Mice deficient in myo1e formed tumors with a more differentiated phenotype relative to the wild-type mice and formed no detectable lung metastases. In the current study, we investigated how the absence of myo1e affects cell migration and invasion in vitro, using the highly invasive and migratory breast cancer cell line, 4T1. 4T1 cells deficient in myo1e exhibited an altered morphology and slower rates of migration in the wound-healing and transwell migration assays compared to the WT 4T1 cells. While integrin trafficking and Golgi reorientation did not appear to be altered upon myo1e loss, we observed lower rates of focal adhesion disassembly in myo1e-deficient cells, which could help explain the cell migration defect.

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