Paquette Mathieu, El-Houjeiri Leeanna, Pause Arnim
Goodman Cancer Research Center, McGill University, Montréal, QC H3A 1A3, Canada.
Department of Biochemistry, McGill University, Montréal, QC H3G 1Y6, Canada.
Cancers (Basel). 2018 Jan 12;10(1):18. doi: 10.3390/cancers10010018.
TOR (target of rapamycin), an evolutionarily-conserved serine/threonine kinase, acts as a central regulator of cell growth, proliferation and survival in response to nutritional status, growth factor, and stress signals. It plays a crucial role in coordinating the balance between cell growth and cell death, depending on cellular conditions and needs. As such, TOR has been identified as a key modulator of autophagy for more than a decade, and several deregulations of this pathway have been implicated in a variety of pathological disorders, including cancer. At the molecular level, autophagy regulates several survival or death signaling pathways that may decide the fate of cancer cells; however, the relationship between autophagy pathways and cancer are still nascent. In this review, we discuss the recent cellular signaling pathways regulated by TOR, their interconnections to autophagy, and the clinical implications of TOR inhibitors in cancer.
雷帕霉素靶蛋白(TOR)是一种在进化上保守的丝氨酸/苏氨酸激酶,作为细胞生长、增殖和存活的核心调节因子,响应营养状态、生长因子和应激信号。它在根据细胞状况和需求协调细胞生长与细胞死亡之间的平衡方面发挥着关键作用。因此,十多年来,TOR已被确定为自噬的关键调节因子,该通路的几种失调与包括癌症在内的多种病理疾病有关。在分子水平上,自噬调节着几种可能决定癌细胞命运的存活或死亡信号通路;然而,自噬通路与癌症之间的关系仍处于初期阶段。在本综述中,我们讨论了最近由TOR调节的细胞信号通路、它们与自噬的相互联系以及TOR抑制剂在癌症中的临床意义。