Heat shock protein 70 positively regulates transforming growth factor-α-induced hepatocellular carcinoma cell migration via the AKT signaling pathway.
Heat shock protein 70 positively regulates transforming growth factor-α-induced hepatocellular carcinoma cell migration via the AKT signaling pathway.
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DOI：
10.1016/j.heliyon.2020.e05002
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发表时间：
2020-09
期刊：
影响因子：
4
通讯作者：
Kozawa O
中科院分区：
文献类型：
--
作者：
Kobayashi K;Matsushima-Nishiwaki R;Yamada N;Migita S;Hioki T;Mizutani D;Kozawa O
热休克蛋白（HSPs）在细胞外应激反应中被诱导，并作为分子伴侣来管理蛋白质的质量。HSP70是一种高度保守的HSP，已被报道与人类癌症细胞的增殖和迁移有关，如口腔癌、前列腺癌、肺癌和肝癌。对于肝细胞癌（HCC），患者肿瘤组织中的HSP70水平明显高于正常肝组织。据报道，HSP70上调HCC的迁移和侵袭。AKT、p38丝裂原活化蛋白激酶（MAPK）、c-jun n-末端激酶（JNK）和rho激酶信号通路调节转化生长因子(TGF)-α-诱导的人hcc源性HuH7细胞的迁移。然而，HSP70在生长因子诱导的HCC迁移中作用的确切机制尚不清楚。因此，本研究探讨HSP70参与TGF-α-诱导的HCC细胞迁移的机制。证实HSP70抑制剂VER155008和YM-08处理及下调HSP70蛋白可显著抑制TGF-α-诱导的HuH7细胞迁移。VER155008和YM-08均能降低TGF-α-诱导的AKT磷酸化，但不影响p38 MAPK、JNK或rho激酶的磷酸化。这些结果强烈提示HSP70通过AKT信号通路正向调节TGF-α-诱导的HCC细胞迁移。细胞生物学;生物化学;癌症研究;肿瘤;实验室医学;一种蛋白激酶;细胞迁移;肝细胞癌;HSP70;转化生长因子-α。
Heat shock proteins (HSPs) are induced in response to extracellular stress and manage the quality of proteins as molecular chaperones. HSP70, a highly conserved HSP, has been reported to correlate with the proliferation and migration of human cancer cells, such as oral, prostate, lung and liver cancer. Regarding hepatocellular carcinoma (HCC), the HSP70 levels in the tumor tissues from patients are significantly higher than those in the normal liver tissues. HSP70 reportedly upregulates the migration and invasion of HCC. The AKT, p38 mitogen-activated protein kinase (MAPK), c-jun N-terminal kinase (JNK) and Rho-kinase signaling pathways regulate the transforming growth factor (TGF)-α-induced migration of human HCC-derived HuH7 cells. However, the exact mechanism underlying the role of HSP70 in growth factor-induced HCC migration remains unclear. Therefore, in the present study, the mechanism underlying the involvement of HSP70 in TGF-α-induced HCC cell migration was investigated. Treatment with the HSP70 inhibitors VER155008 and YM-08 and the downregulation of HSP70 protein were confirmed to significantly suppress the TGF-α-induced cell migration of HuH7 cells. Both VER155008 and YM-08 reduced the TGF-α-induced phosphorylation of AKT without affecting the phosphorylation of p38 MAPK, JNK or Rho-kinase. These results strongly suggest that HSP70 positively regulates the TGF-α-induced migration of HCC cells via the AKT signaling pathway. Cell biology; Biochemistry; Cancer research; Oncology; Laboratory medicine; AKT; Cell migration; HCC; HSP70; TGF-α.
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影响因子：
81.5
作者：
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通讯作者：
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影响因子：
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