The mTOR Signaling Pathway Interacts with the ER Stress Response and the Unfolded Protein Response in Cancer

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 cruc...

Full description

Saved in:
Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 2023-08, Vol.83 (15), p.2450-2460
Main Authors: Mafi, Sahar, Ahmadi, Elham, Meehan, Eileen, Chiari, Conner, Mansoori, Behzad, Sadeghi, Hossein, Milani, Sahar, Jafarinia, Morteza, Taeb, Shahram, Mafakheri Bashmagh, Bayan, Mansoorian, Seyed Mohammad Ali, Soltani-Zangbar, Mohammad Sadegh, Wang, Kepeng, Rostamzadeh, Davoud
Format: Article
Language:English
Subjects:
Endoplasmic Reticulum Stress
Humans
Neoplasms
Phosphatidylinositol 3-Kinases - metabolism
Signal Transduction - physiology
TOR Serine-Threonine Kinases - metabolism
Unfolded Protein Response
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0008-5472
1538-7445
DOI:10.1158/0008-5472.CAN-22-3032