Overexpression of PITPNM3 promotes hepatocellular carcinoma cell metastasis
Overexpression of PITPNM3 promotes hepatocellular carcinoma cell metastasis
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PITPNM3过表达促进肝癌细胞转移
DOI：
10.1007/s11434-014-0183-z
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发表时间：
2014-04-01
影响因子：
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通讯作者：
Liu, Yujie
中科院分区：
文献类型：
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作者：
He, Chonghua;Su, Shicheng;Liu, Yujie
先前的研究表明，C-C趋化因子（C-C基序）配体18（CCL18）能够通过与乳腺癌细胞中受体膜相关磷脂酰肌醇转移蛋白3（PITPNM3）相互作用来诱导肿瘤细胞侵袭和转移。本研究旨在探讨肝细胞癌（HCC）中PITPNM3表达与转移之间的相关性。采用实时定量聚合酶链反应和Western blot检测患者样本和HCC细胞系中PITPNM3的表达模式。进行伤口愈合和transwell小室实验来评估HCC细胞的迁移和侵袭能力，并通过Western blot和免疫荧光检测PITPNM3下游信号蛋白的激活。结果显示，与匹配的正常肝组织相比，PITPNM3 在 HCC 组织中表达上调。通过特异性siRNA沉默PITPNM3的表达显着减弱HCC细胞的侵袭和转移能力，而PITPNM3的上调显着增加HCC细胞的迁移性。此外，抑制 PITPNM3 的表达会抑制 Pyk2、FAK 和 Src 的激活，而 PITPNM3 的过表达会增强 HCC 细胞中 FAK 和 Src 的磷酸化。此外，抑制Pyk2也会损害整合素的聚集。这些结果表明 PITPNM3 是 HCC 迁移和侵袭的重要决定因素。
A previous study indicated that C-C chemokine (C-C motif) ligand 18 (CCL18) is capable of inducing tumor cell invasion and metastasis by interacting with receptor membrane-associated phosphatidylinositol transfer protein 3 (PITPNM3) in breast cancer cells. The present study aims to investigate the correlation between the PITPNM3 expression and metastasis in hepatocellular carcinoma (HCC). Real-time quantitative polymerase chain reaction and Western blot were performed to detect the expression pattern of PITPNM3 in patient samples and HCC cell lines. Wound-healing and transwell chamber assays were performed to assess the migration and invasiveness of HCC cells, and the activation of the signaling protein downstream of PITPNM3 was also detected by Western blot and immunofluorescence. The results revealed that PITPNM3 was upregulated in HCC tissue compared to matched normal liver tissue. Silencing the expression of PITPNM3 by specific siRNAs markedly attenuated the invasive and metastatic abilities of HCC cells, whereas the upregulation of PITPNM3 significantly increased HCC cell mobility. Furthermore, inhibiting the expression of PITPNM3 suppressed the activation of Pyk2, FAK, and Src, while overexpression of PITPNM3 enhanced the phosphorylation of FAK and Src in HCC cells. Besides, suppression of Pyk2 can also impair the clustering of integrin. These results imply that PITPNM3 is a vital determinant of HCC migration and invasion.