Pathways that regulate autophagy and their role in mediating tumor response to treatment.
In addition to their role in cellular homeostasis, pathways that regulate autophagy affect both tumorigenesis and tumor response to treatment. Therefore, understanding the regulation of autophagy in treated cancer cells is relevant to the discovery of molecular targets for the development of anti-cancer drugs. Our recent report points to radiation-induced inactivation of the mTOR pathway as an underlying mechanism of radiation-induced autophagy in the human breast cancer cell line MCF-7. Most importantly, radiation-induced inactivation of this pathway was detrimental to cell survival and was associated with reversal of mitochondrial ATPase activity and mitochondrial hyperpolarization, decreased level of eukaryotic initiation factor 4G (eIF4G) and increased phosphorylation of p53. Future analysis of the interrelationship among these events and the role each of them plays in cell survival following radiation will increase our ability to employ the mTOR pathway in anti-cancer therapy.
Paglin
Shoshana
S
The Institute of Oncology, Sheba Medical Center, Tel-Hashomer, Ramat-Gan, Israel. s_paglin@netvision.net.il
Yahalom
Joachim
J
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001343:Autophagy / Q000502:physiology* / Q000528:radiation effects; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000532:radiotherapy; D011494:Protein Kinases / Q000378:metabolism; D015398:Signal Transduction / Q000528:radiation effects*; D058570:TOR Serine-Threonine Kinases
D000970:Antineoplastic Agents; D011494:Protein Kinases; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases