Department of Pathophysiology, The Key Immunopathology Laboratory of Guangdong Province, Shantou University Medical College, Shantou, Guangdong Province, 515041, China.
Department of Prepotency and Genetics, Affiliated Hospital of Guilin Medical University, Guilin, Guangxi, 541001, China.
Sci Rep. 2018 Sep 26;8(1):14402. doi: 10.1038/s41598-018-32698-3.
TFPI-2 has been recognized as a potent tumor suppressor gene. Low expression of TFPI-2 results in enhanced growth and metastasis of a variety of human tumors. In the present study, we investigated the mechanism responsible for the tumor suppressive effect of TFPI-2. Overexpression of TFPI-2 decreased phosphorylation of ERK1/2 and the translocation of p-ERK1/2 from cytoplasm into the nucleus, and eventually resulted in a reduced cell proliferation. Immunoprecipitation assays identified myosin-9 and actinin-4 as TFPI-2-interacting proteins. Full-length TFPI-2 was required for binding to actinin-4, whereas the N + KD1 regions of TFPI-2 were sufficient to interact with myosin-9. Although overexpression of TFPI-2 or TFPI-2/N + KD1 does not affect the expression of actinin-4 and myosin-9, it inhibits the migration and invasion of human breast cancer cells. Our results suggest that TFPI-2 suppresses cancer cell proliferation and invasion partly through the regulation of the ERK1/2 signaling and through interactions with myosin-9 and actinin-4.
TFPI-2 已被确认为一种有效的肿瘤抑制基因。TFPI-2 的低表达导致多种人类肿瘤的生长和转移增强。在本研究中，我们研究了 TFPI-2 的肿瘤抑制作用的机制。TFPI-2 的过表达降低了 ERK1/2 的磷酸化和 p-ERK1/2 从细胞质向细胞核的易位，最终导致细胞增殖减少。免疫沉淀实验鉴定出肌球蛋白-9 和肌动蛋白-4 是 TFPI-2 的相互作用蛋白。全长 TFPI-2 与肌动蛋白-4 结合所必需的，而 TFPI-2 的 N+KD1 区域足以与肌球蛋白-9 相互作用。尽管 TFPI-2 或 TFPI-2/N+KD1 的过表达不会影响肌动蛋白-4 和肌球蛋白-9 的表达，但它抑制了人乳腺癌细胞的迁移和侵袭。我们的结果表明，TFPI-2 通过调节 ERK1/2 信号通路以及与肌球蛋白-9 和肌动蛋白-4 的相互作用，部分抑制癌细胞的增殖和侵袭。
