PTEN is required for the migration and invasion of Ras‐transformed MDCK cells
PTEN is required for the migration and invasion of Ras‐transformed MDCK cells
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DOI：
10.1002/1873-3468.14053
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发表时间：
2021-02
期刊：
影响因子：
3.5
通讯作者：
Lu Yan;K. Tsujita;Yasuyuki Fujita;T. Itoh
中科院分区：
文献类型：
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作者：
Lu Yan;K. Tsujita;Yasuyuki Fujita;T. Itoh
分布在质膜特定部位的磷酸肌醇之间的平衡导致极化肌动蛋白聚合。致癌性转化通过调节磷酸肌醇3-激酶（PI 3 K）和10号染色体上缺失的磷酸酶和张力蛋白同源物（PTEN）来影响这种平衡，导致癌细胞的转移行为。在这里，我们表明，PTEN肿瘤抑制基因是上皮癌细胞侵袭所必需的。Ras转化的MDCK细胞中PTEN的缺失抑制了它们在胶原凝胶中的迁移表型和通过Matrigel的侵袭。拯救实验表明需要C2结构域介导的PTEN膜募集，这通常在入侵癌细胞的后侧观察到。这些发现支持了PTEN在抑制上皮癌细胞有效迁移所必需的不需要的前缘中的作用。
The balance between phosphoinositides distributed at specific sites in the plasma membrane causes polarized actin polymerization. Oncogenic transformations affect this balance by regulating phosphoinositide 3‐kinase (PI3K) and phosphatase and tensin homolog deleted on chromosome 10 (PTEN), causing metastatic behavior in cancer cells. Here, we show that the PTEN tumor suppressor gene is required for epithelial cancer cell invasion. Loss of PTEN in Ras‐transformed MDCK cells suppressed their migratory phenotype in collagen gel and invasion through Matrigel. Rescue experiments showed a requirement for the C2 domain‐mediated membrane recruitment of PTEN, which is typically observed at the rear side of invading cancer cells. These findings support the role of PTEN in suppression of unwanted leading edges necessary for efficient migration of epithelial cancer cells.