GP73-mediated secretion of AFP and GP73 promotes proliferation and metastasis of hepatocellular carcinoma cells.
GP73-mediated secretion of AFP and GP73 promotes proliferation and metastasis of hepatocellular carcinoma cells.
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GP73介导的AFP和GP73的分泌促进肝细胞癌细胞的增殖和转移。
DOI：
10.1038/s41389-021-00358-3
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发表时间：
2021-10-14
期刊：
影响因子：
6.2
通讯作者：
Zhang X
中科院分区：
文献类型：
--
作者：
Liu Y;Wang J;Yang R;Cheng Y;Zhou Y;Li H;Jiang W;Zhang X
高尔基体蛋白73（GP73）和甲胎蛋白（AFP）是诊断肝细胞癌（HCC）的生物标志物，其血清水平与患者的预后相关。然而，这些相关性的机制是未知的。在这里，我们表明，GP73通过直接结合AFP增加AFP的分泌，从而促进表达AFP及其受体（AFPR）的HCC细胞的增殖和转移。细胞外GP73对肝癌细胞增殖和转移的作用不依赖于AFP和AFPR。此外，细胞外AFP和GP 73协同增强HCC细胞的恶性表型。此外，细胞外GP73和AFP抑制索拉非尼的抗肿瘤作用，并协同增加肝癌细胞的耐药性。这些发现揭示了GP 73介导的AFP分泌机制及其对肝癌细胞恶性表型的影响，为肝癌的诊断和治疗提供了全面的理论依据，并确定了潜在的药物靶点。
Golgi protein 73 (GP73) and alpha fetoprotein (AFP) serve as biomarkers for the diagnosis of hepatocellular carcinoma (HCC), and their serum levels correlate with patients’ outcomes. However, the mechanisms underlying these correlations are unknown. Here we show that GP73 increased the secretion of AFP through direct binding to AFP, thereby promoting the proliferation and metastasis of HCC cells that expressed AFP and its receptor (AFPR). Extracellular GP73 contributed to the proliferation and metastasis of HCC cells independent of AFP and AFPR. Moreover, extracellular AFP and GP73 synergized to enhance the malignant phenotype of HCC cells. Furthermore, extracellular GP73 and AFP inhibited the antitumor effects of sorafenib and synergistically increased the drug resistance of HCC cells. These findings, which reveal the mechanism of GP73-mediated secretion of AFP and its effects on the malignant phenotype of HCC cells, provide a comprehensive theoretical basis for the diagnosis and treatment of HCC and identify potential drug targets.
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影响因子：
6.2
作者：
Liu, Yiming;Zhou, Sining;Zhou, Linfu
通讯作者：
Zhou, Linfu
DOI：
10.3233/cbm-2010-0190
发表时间：
2010
期刊：
Cancer biomarkers : section A of Disease markers
影响因子：
--
作者：
Hann HW;Wang M;Hafner J;Long RE;Kim SH;Ahn M;Park S;Comunale MA;Block TM;Mehta A
通讯作者：
Mehta A
DOI：
10.1038/s41379-018-0110-y
发表时间：
2018-12
期刊：
Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc
影响因子：
--
作者：
Rindi G;Klimstra DS;Abedi-Ardekani B;Asa SL;Bosman FT;Brambilla E;Busam KJ;de Krijger RR;Dietel M;El-Naggar AK;Fernandez-Cuesta L;Klöppel G;McCluggage WG;Moch H;Ohgaki H;Rakha EA;Reed NS;Rous BA;Sasano H;Scarpa A;Scoazec JY;Travis WD;Tallini G;Trouillas J;van Krieken JH;Cree IA
通讯作者：
Cree IA
影响因子：
158.5
作者：
Llovet, Josep M.;Ricci, Sergio;Bruix, Jordi
通讯作者：
Bruix, Jordi
影响因子：
4.3
作者：
Gatselis, Nikolaos K.;Tornai, Tamas;Dalekos, George N.
通讯作者：
Dalekos, George N.