Hua Hong-Wei, Jiang Feng, Huang Qian, Liao Zhi-Jun, Ding Gang
Department of Oncology, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200093, China.
Tumour Biol. 2015 Jan;36(1):303-13. doi: 10.1007/s13277-014-2633-2. Epub 2014 Sep 25.
Secreted protein, acidic and rich in cysteine (SPARC), a calcium-binding matricellular glycoprotein, is implicated in the progression of many cancers. Currently, there is growing evidence for important functions of SPARC in a variety of cancers and its role in cancer depends on tumor types. In this study, we reported SPARC negatively regulated glucose metabolism in hepatocellular carcinoma (HCC). Overexpression of SPARC inhibited glucose uptake and lactate product through downregulation of key enzymes of glucose metabolism. On the other hand, knock down of SPARC reversed the phenotypes. Meanwhile, exogenous expression of SPARC in HepG2 cells resulted in tolerance to low glucose and was correlated with AMPK pathway. Interestingly, the 5-fluorouracil (5-FU)-resistant HepG2 cells showed increased glucose metabolism and downregulated SPARC levels. Finally, we reported the overexpression of SPARC re-sensitize 5-FU-resistant cells to 5-FU through inhibition of glycolysis both in vitro and in vivo. Our study proposed a novel function of SPARC in the regulation of glucose metabolism in hepatocellular carcinoma and will facilitate the development of therapeutic strategies for the treatments of liver tumor patients.
分泌性蛋白质，富含酸性和半胱氨酸（SPARC），一种钙结合基质细胞糖蛋白，与多种癌症的进展有关。目前，越来越多的证据表明SPARC在多种癌症中具有重要功能，其在癌症中的作用取决于肿瘤类型。在本研究中，我们报道了SPARC在肝细胞癌（HCC）中对葡萄糖代谢具有负调控作用。SPARC的过表达通过下调葡萄糖代谢关键酶抑制葡萄糖摄取和乳酸生成。另一方面，敲低SPARC可逆转这些表型。同时，在HepG2细胞中外源表达SPARC导致对低葡萄糖的耐受性，并与AMPK途径相关。有趣的是，5-氟尿嘧啶（5-FU）耐药的HepG2细胞显示葡萄糖代谢增加且SPARC水平下调。最后，我们报道SPARC的过表达通过在体外和体内抑制糖酵解使5-FU耐药细胞对5-FU重新敏感。我们的研究提出了SPARC在肝细胞癌葡萄糖代谢调节中的新功能，并将促进肝肿瘤患者治疗策略的发展。
