Wang Yue, Peng Jianing, Yang Dengyuan, Xing Zhongjie, Jiang Bo, Ding Xu, Jiang Chaoyu, Ouyang Bing, Su Lei
Department of Surgery, Nanjing Central Hospital, Nanjing, China.
Division of Biosciences, University College London, London, United Kingdom.
Front Oncol. 2024 May 7;14:1383809. doi: 10.3389/fonc.2024.1383809. eCollection 2024.
PGC1α, a central player in mitochondrial biology, holds a complex role in the metabolic shifts seen in cancer cells. While its dysregulation is common across major cancers, its impact varies. In some cases, downregulation promotes aerobic glycolysis and progression, whereas in others, overexpression escalates respiration and aggression. PGC1α's interactions with distinct signaling pathways and transcription factors further diversify its roles, often in a tissue-specific manner. Understanding these multifaceted functions could unlock innovative therapeutic strategies. However, challenges exist in managing the metabolic adaptability of cancer cells and refining PGC1α-targeted approaches. This review aims to collate and present the current knowledge on the expression patterns, regulators, binding partners, and roles of PGC1α in diverse cancers. We examined PGC1α's tissue-specific functions and elucidated its dual nature as both a potential tumor suppressor and an oncogenic collaborator. In cancers where PGC1α is tumor-suppressive, reinstating its levels could halt cell proliferation and invasion, and make the cells more receptive to chemotherapy. In cancers where the opposite is true, halting PGC1α's upregulation can be beneficial as it promotes oxidative phosphorylation, allows cancer cells to adapt to stress, and promotes a more aggressive cancer phenotype. Thus, to target PGC1α effectively, understanding its nuanced role in each cancer subtype is indispensable. This can pave the way for significant strides in the field of oncology.
PGC1α是线粒体生物学的核心参与者，在癌细胞的代谢转变中发挥着复杂的作用。虽然其失调在主要癌症中很常见，但其影响各不相同。在某些情况下，下调会促进有氧糖酵解和进展，而在其他情况下，过表达会加剧呼吸作用和侵袭性。PGC1α与不同信号通路和转录因子的相互作用进一步使其作用多样化，通常以组织特异性的方式。了解这些多方面的功能可能会开启创新的治疗策略。然而，在管理癌细胞的代谢适应性和完善针对PGC1α的方法方面存在挑战。本综述旨在整理并呈现目前关于PGC1α在多种癌症中的表达模式、调节因子、结合伙伴和作用的知识。我们研究了PGC1α的组织特异性功能，并阐明了其作为潜在肿瘤抑制因子和致癌协同因子的双重性质。在PGC1α具有肿瘤抑制作用的癌症中，恢复其水平可能会阻止细胞增殖和侵袭，并使细胞对化疗更敏感。在相反情况的癌症中，阻止PGC1α的上调可能是有益的，因为它促进氧化磷酸化，使癌细胞能够适应压力，并促进更具侵袭性的癌症表型。因此，要有效地靶向PGC1α，了解其在每种癌症亚型中的细微作用是必不可少的。这可以为肿瘤学领域的重大进展铺平道路。
