Autophagy and cancer: dynamism of the metabolism of tumor cells and tissues.
Autophagy is a dynamic process involving the bulk degradation of cytoplasmic organelles and proteins. Based on the function of "cellular recycling", autophagy plays key roles in the quality control of cellular components as well as supplying nutrients and materials for newly constructed structures in cells under metabolic stresses. The physiological relevance of autophagy in tumor formation and progression is still controversial. The cytoprotective function of autophagy in cells subjected to starvation might enhance the prolonged survival of tumor cells that are often exposed to metabolic stresses in vivo. Meanwhile, a tumor-suppressive function of autophagy has also been suggested. Autophagy-related cell death has been regarded as a primary mechanism for tumor suppression. In addition, the loss of autophagy induced genome instability and significant necrosis with inflammation in transplanted mouse tumor models, suggesting an additional function of autophagy in the suppression of tumor formation and growth. Until now, investigations supporting and proving the above possibilities have not been fully completed using clinical samples and equivalent animal models. Though monitoring and the interpretation of autophagy dynamism in tumor tissues are still technically difficult, identifying the autophagic activity in clinical samples might be necessary to clarify the pathophysiological relevance of autophagy in tumor formation and progression as well as to develop new therapeutic strategies based on the regulation of autophagy.
Tsuchihara
Katsuya
K
Cancer Physiology Project, Research Center for Innovative oncology, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa, Chiba 277-8577, Japan.
Fujii
Satoshi
S
Pathology Division, Research Center for Innovative Oncology, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa, Chiba 277-8577, Japan.
Esumi
Hiroyasu
H
Cancer Physiology Project, Research Center for Innovative oncology, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa, Chiba 277-8577, Japan. Electronic address: hesumi@east.ncc.go.jp.
D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000502:physiology; D001343:Autophagy; D000071186:Beclin-1; D004734:Energy Metabolism; D006801:Humans; D008565:Membrane Proteins / Q000502:physiology; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology; D011494:Protein Kinases / Q000502:physiology; D058570:TOR Serine-Threonine Kinases; D016159:Tumor Suppressor Protein p53 / Q000502:physiology; D025521:Tumor Suppressor Proteins / Q000502:physiology
D051017:Apoptosis Regulatory Proteins; C491997:BECN1 protein, human; D000071186:Beclin-1; D008565:Membrane Proteins; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; C408122:UVRAG protein, human; D011494:Protein Kinases; C546842:MTOR protein, human; C546843:mTOR protein, mouse; D058570:TOR Serine-Threonine Kinases