Garone Michael E, Chase Sharon E, Zhang Chunling, Krendel Mira
Department of Cell and Developmental Biology, State University of New York Upstate Medical University, Syracuse, New York, USA.
Department of Neuroscience and Physiology, State University of New York Upstate Medical University, Syracuse, New York, USA.
Cytoskeleton (Hoboken). 2024 Dec;81(12):723-736. doi: 10.1002/cm.21819. Epub 2023 Dec 23.
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.
乳腺癌细胞转移至远处组织部位是导致大多数乳腺癌相关死亡的原因。此前,我们使用小鼠乳腺肿瘤病毒-多瘤病毒中间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,缺乏myo1e的小鼠形成的肿瘤具有更分化的表型,且未形成可检测到的肺转移。在本研究中,我们使用高侵袭性和迁移性的乳腺癌细胞系4T1,研究了myo1e缺失如何影响体外细胞迁移和侵袭。与野生型4T1细胞相比,缺乏myo1e的4T1细胞在伤口愈合和Transwell迁移试验中表现出形态改变和迁移速率减慢。虽然在myo1e缺失后整合素运输和高尔基体重新定向似乎没有改变,但我们观察到myo1e缺陷细胞中粘着斑解体的速率较低,这可能有助于解释细胞迁移缺陷。