PDF(Pubmed)
Abstract：
The development and growth of cancer is fundamentally dependent on pro-tumor changes in metabolism. Cancer cells generally shift away from oxidative phosphorylation as the primary source of energy and rely more heavily on glycolysis. Receptor tyrosine kinases (RTKs) are a type of receptor that is implicated in this shift to pro-tumor metabolism. RTKs are important drivers of cancer growth and metastasis. One such family of RTKs is the MET family, which consists of MET and RON (MST1R). The overexpression of either MET or RON has been associated with worse cancer patient prognosis in a variety of tumor types. Both MET and RON signaling promote increased glycolysis by upregulating the expression of key glycolytic enzymes via increased MYC transcription factor activity. Additionally, both MET and RON signaling promote increased cholesterol biosynthesis downstream of glycolysis by upregulating the expression of SREBP2-induced cholesterol biosynthesis enzymes via CTTNB1. These changes in metabolism, driven by RTK activity, provide potential targets in limiting tumor growth and metastasis via pharmacological inhibition or modifications in diet. This review summarizes pro-tumor changes in metabolism driven by the MET family of RTKs. In doing so, we will offer our unique perspective on metabolic pathways that drive worse patient prognosis and provide suggestions for future study.
摘要：
癌症的发展和生长从根本上取决于代谢中的促肿瘤变化。癌细胞通常从氧化磷酸化转变为主要能量来源，并更严重地依赖糖酵解。受体酪氨酸激酶(RTKs)是一种类型的受体,其与向促肿瘤代谢的这种转变有关。RTK是癌症生长和转移的重要驱动因素。一个这样的RTK家族是MET家族，由MET和RON(MST1R)组成。在多种肿瘤类型中,MET或RON的过表达与较差的癌症患者预后相关。MET和RON信号通过增加MYC转录因子活性上调关键糖酵解酶的表达来促进糖酵解增加。此外,MET和RON信号通过上调SREBP2诱导的胆固醇生物合成酶的表达,促进糖酵解下游胆固醇生物合成的增加。这些新陈代谢的变化，由RTK活动驱动，通过药理学抑制或饮食修饰，为限制肿瘤生长和转移提供潜在的靶标。本文综述了由RTK的MET家族驱动的促肿瘤代谢变化。在这样做的时候，我们将就导致患者预后恶化的代谢途径提供我们独特的观点，并为未来的研究提供建议。
