Medicinal Plants Research Center, Yasuj University of Medical Sciences, Yasuj, Iran.
Department of Clinical Biochemistry, Yasuj University of Medical Sciences, Yasuj, Iran.
Cancer Res. 2023 Aug 1;83(15):2450-2460. doi: 10.1158/0008-5472.CAN-22-3032.
The mTOR complex 1 (mTORC1) coordinates several important environmental and intracellular cues to control a variety of biological processes, such as cell growth, survival, autophagy, and metabolism, in response to energy levels, growth signals, and nutrients. The endoplasmic reticulum (ER) is a crucial intracellular organelle that is essential for numerous cellular functions, including the synthesis, folding, and modification of newly synthesized proteins, stress responsiveness, and maintainence of cellular homeostasis. mTOR-mediated upregulation of protein synthesis induces the accumulation of misfolded or unfolded proteins in the ER lumen, which induces ER stress, leading to activation of the unfolded protein response (UPR) pathway. Reciprocally, ER stress regulates the PI3K/AKT/mTOR signaling pathway. Therefore, under pathologic conditions, the cross-talk between the mTOR and UPR signaling pathways during cellular stress can critically affect cancer cell fate and may be involved in the pathogenesis and therapeutic outcome of cancer. Here, we discuss accumulating evidence showing the mechanism of action, interconnections, and molecular links between mTOR signaling and ER stress in tumorigenesis and highlights potential therapeutic implications for numerous cancers.
mTOR 复合物 1（mTORC1）协调多种重要的环境和细胞内信号，以响应能量水平、生长信号和营养物质来控制多种生物过程，如细胞生长、存活、自噬和代谢。内质网（ER）是一种至关重要的细胞内细胞器，对于许多细胞功能至关重要，包括新合成蛋白质的合成、折叠和修饰、应激反应以及维持细胞内稳态。mTOR 介导的蛋白质合成上调会导致内质网腔中错误折叠或未折叠蛋白质的积累，从而诱导内质网应激，导致未折叠蛋白反应（UPR）途径的激活。反过来，内质网应激调节 PI3K/AKT/mTOR 信号通路。因此，在病理条件下，细胞应激过程中 mTOR 和 UPR 信号通路之间的串扰可能会严重影响癌细胞的命运，并可能参与癌症的发病机制和治疗结果。在这里，我们讨论了越来越多的证据，这些证据表明了 mTOR 信号和肿瘤发生过程中 ER 应激之间的作用机制、相互联系和分子联系，并强调了针对多种癌症的潜在治疗意义。
