Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science, Bangalore, 560012, India.
Mol Cell Biochem. 2021 Jun;476(6):2269-2282. doi: 10.1007/s11010-021-04088-3. Epub 2021 Feb 11.
Since its initial discovery as the gene altered in Tuberous Sclerosis Complex (TSC), an autosomal dominant disorder, the interest in TSC1 (Tuberous Sclerosis Complex 1) has steadily risen. TSC1, an essential component of the pro-survival PI3K/AKT/MTOR signaling pathway, plays an important role in processes like development, cell growth and proliferation, survival, autophagy and cilia development by co-operating with a variety of regulatory molecules. Recent studies have emphasized the tumor suppressive role of TSC1 in several human cancers including liver, lung, bladder, breast, ovarian, and pancreatic cancers. TSC1 perceives inputs from various signaling pathways, including TNF-α/IKK-β, TGF-β-Smad2/3, AKT/Foxo/Bim, Wnt/β-catenin/Notch, and MTOR/Mdm2/p53 axis, thereby regulating cancer cell proliferation, metabolism, migration, invasion, and immune regulation. This review provides a first comprehensive evaluation of TSC1 and illuminates its diverse functions apart from its involvement in TSC genetic disorder. Further, we have summarized the physiological functions of TSC1 in various cellular events and conditions whose dysregulation may lead to several pathological manifestations including cancer.
自其首次被发现是结节性硬化症（TSC）的基因改变以来，这种常染色体显性遗传疾病引起了人们的持续关注。TSC1 是抗生存 PI3K/AKT/MTOR 信号通路的重要组成部分，通过与各种调节分子合作，在发育、细胞生长和增殖、生存、自噬和纤毛发育等过程中发挥重要作用。最近的研究强调了 TSC1 在包括肝癌、肺癌、膀胱癌、乳腺癌、卵巢癌和胰腺癌在内的多种人类癌症中的肿瘤抑制作用。TSC1 感知来自各种信号通路的输入，包括 TNF-α/IKK-β、TGF-β-Smad2/3、AKT/Foxo/Bim、Wnt/β-catenin/Notch 和 MTOR/Mdm2/p53 轴，从而调节癌细胞的增殖、代谢、迁移、侵袭和免疫调节。这篇综述首次对 TSC1 进行了全面评估，阐明了它在 TSC 遗传疾病之外的多种功能。此外，我们总结了 TSC1 在各种细胞事件和条件中的生理功能，其失调可能导致包括癌症在内的几种病理表现。
