Tianyi Wang1, Conghe Liu1, Lili Jia2. 1. NHC Key Laboratory of Radiobiology (Ministry of Health), School of Public Health, Jilin University, 1163 Xinmin Street, Changchun, 130021, People's Republic of China. 2. NHC Key Laboratory of Radiobiology (Ministry of Health), School of Public Health, Jilin University, 1163 Xinmin Street, Changchun, 130021, People's Republic of China. jiall@jlu.edu.cn.
Abstract
PURPOSE: Autophagy, as a highly conserved cellular degradation and recycling process, plays an important part in maintaining cellular homeostasis. PKC signaling is involved in multiple pathways including cell cycle progression, tumorigenesis, migration and autophagy. METHODS: Literatures about PKC and autophagy from PubMed databases were reviewed in this study. RESULTS: Studies regarding the association of PKC and autophagy remain debatable. Different duration of the stimulation of autophagy and distinct cell contexts result in different function of PKC in regulating autophagy. The subcellular localization of PKCs and their downstream regulators may influence the autophagy regulation as well. As important intracellular components, the mitochondria play an important role in regulating autophagy, by metabolic modulation and structural derangement. CONCLUSION: Phase II studies regarding PKC-β inhibitor, enzastaurin, showed promising results in MCL, DLBCL and recurrent high-grade gliomas. However, the detailed mechanism is still in need. The mechanism of PKC-β in mediating autophagy in lymphoma and high-grade gliomas remains elusive as well. Moreover, several studies were in agreement that rottlerin enhanced autophagy in breast cancer cells, which warrants further clinical studies to verify PKC-δ as a therapeutic target. Thus, identifying the function of PKC in modulating autophagy and conducting related clinical studies help find novel target for chemotherapy.
PURPOSE: Autophagy, as a highly conserved cellular degradation and recycling process, plays an important part in maintaining cellular homeostasis. PKC signaling is involved in multiple pathways including cell cycle progression, tumorigenesis, migration and autophagy. METHODS: Literatures about PKC and autophagy from PubMed databases were reviewed in this study. RESULTS: Studies regarding the association of PKC and autophagy remain debatable. Different duration of the stimulation of autophagy and distinct cell contexts result in different function of PKC in regulating autophagy. The subcellular localization of PKCs and their downstream regulators may influence the autophagy regulation as well. As important intracellular components, the mitochondria play an important role in regulating autophagy, by metabolic modulation and structural derangement. CONCLUSION: Phase II studies regarding PKC-β inhibitor, enzastaurin, showed promising results in MCL, DLBCL and recurrent high-grade gliomas. However, the detailed mechanism is still in need. The mechanism of PKC-β in mediating autophagy in lymphoma and high-grade gliomas remains elusive as well. Moreover, several studies were in agreement that rottlerin enhanced autophagy in breast cancer cells, which warrants further clinical studies to verify PKC-δ as a therapeutic target. Thus, identifying the function of PKC in modulating autophagy and conducting related clinical studies help find novel target for chemotherapy.
Authors: Michael J Robertson; Brad S Kahl; Julie M Vose; Sven de Vos; Mary Laughlin; Patrick J Flynn; Kendrith Rowland; Jose C Cruz; Stuart L Goldberg; Luna Musib; Christelle Darstein; Nathan Enas; Jeffery L Kutok; Jon C Aster; Donna Neuberg; Kerry J Savage; Ann LaCasce; Donald Thornton; Christopher A Slapak; Margaret A Shipp Journal: J Clin Oncol Date: 2007-03-26 Impact factor: 44.544
Authors: Damián E Berardi; Carolina Flumian; Cristina E Rodriguez; María I Díaz Bessone; Stefano M Cirigliano; Elisa D Bal de Kier Joffé; Gabriel L Fiszman; Alejandro J Urtreger; Laura B Todaro Journal: J Cell Biochem Date: 2015-09-10 Impact factor: 4.429