CKAP4 inhibited growth and metastasis of hepatocellular carcinoma through regulating EGFR signaling
CKAP4 inhibited growth and metastasis of hepatocellular carcinoma through regulating EGFR signaling
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CKAP4通过调节EGFR信号抑制肝细胞癌的生长和转移
DOI：
10.1007/s13277-014-2000-3
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发表时间：
2014-08-01
期刊：
影响因子：
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通讯作者：
Wang, Hong-yang
中科院分区：
文献类型：
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作者：
Li, Shuang-xi;Liu, Li-juan;Wang, Hong-yang
CKAP 4是一种II型跨膜蛋白，通过与抗增殖因子（anti-proliferative factor，APF）结合，维持内质网结构，抑制膀胱癌细胞增殖。然而，CKAP 4在肝癌进展中的生物学功能尚未得到明确证实。在本研究中，我们敲低或过表达CKAP 4在肝细胞癌（HCC）细胞和细胞增殖，侵袭和迁移能力进行了研究CCK-8和transwell测定。采用小鼠体内肿瘤模型研究CKAP 4在肝癌生长和转移中的作用。数据证明，具有高CKAP 4水平的HCC细胞具有低增殖能力以及低侵袭潜力的特征。有趣的是，我们发现CKAP 4抑制了上皮生长因子受体（EGFR）信号的激活，这可能部分解释了CKAP 4在HCC细胞生物学行为中的作用。进一步研究发现，CKAP 4在基础状态下可与EGFR结合，EGF刺激后复合物减少，导致EGFR释放到胞浆中。因此，我们首次证明了CKAP 4的表达调节HCC的进展和转移的新机制，并且它可能在这种肿瘤中提供治疗价值。
CKAP4, one kind of type II trans-membrane protein, plays an important role to maintain endoplasmic reticulum structure and inhibits the proliferation of bladder cancer cells by combining its ligand anti-proliferative factor (APF). However, the biological function of CKAP4 in the progression of liver cancer has not been clearly demonstrated. In the present study, we knocked down or overexpressed CKAP4 in hepatocellular carcinoma (HCC) cells and cell proliferation, invasion, and migration capacities were investigated by CCK-8 and transwell assays. In vivo tumor model in mice was used to evaluate the role of CKAP4 on growth and metastasis of HCC. The data documented that HCC cells with high CKAP4 levels were featured by low proliferation capability as well as low invasion potential. Interestingly, we found that CKAP4 suppressed the activation of epithelial growth factor receptor (EGFR) signaling, which may partly explain the role of CKAP4 in cell biological behavior of HCC. Further study revealed that CKAP4 could associate with EGFR at basal status and the complex was reduced upon EGF stimulation, leading to release EGFR into cytoplasm. Thus, we demonstrate the novel mechanism, for the first time, expression of CKAP4 regulates progression and metastasis of HCC and it may provide therapeutic values in this tumor.