Inhibition of atypical protein kinase Cι induces apoptosis through autophagic degradation of β-catenin in esophageal cancer cells.
Atypical protein kinase Cι (PKCι) has been identified as an oncoprotein in esophageal squamous cell carcinomas. However, the mechanisms underlying the role of PKCι in this disease remain unclear. In the present work, we found that inhibition of PKCι expression by RNAi induced apoptosis via the down-regulation of β-catenin in esophageal cancer cells. Furthermore, we found that PKCι regulated β-catenin in an autophagy dependent way. Since down-regulation of β-catenin induced by knockdown of PKCι could be rescued by autophagy inhibition; knockdown of PKCι activated autophagy and promoted the recruitment of β-catenin into autophagosome. These results suggested that PKCι positively regulated β-catenin through negatively regulated autophagy and depletion of PKCι promoted apoptosis via autophagic degradation of β-catenin in esophageal cancer cells. These data provide new insights into PKCι signaling in human cancer.
State Key Laboratory of Molecular Oncology, Cancer Institute (Hospital), Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
Bo-Shi
BS
Wang
Yang
Y
Yang
Hai-Zhen
HZ
Lu
Li
L
Shang
Yu
Y
Zhang
Jia-Jie
JJ
Hao
Zhi-Zhou
ZZ
Shi
Xiao-Min
XM
Wang
Yi-Zhen
YZ
Liu
Qi-Min
QM
Zhan
Xue-Mei
XM
Jia
Ming-Rong
MR
Wang
D017209:Apoptosis / Q000235:genetics*; D001343:Autophagy / Q000235:genetics*; D000071187:Autophagy-Related Protein 5; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D015536:Down-Regulation; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000473:pathology; D000077277:Esophageal Squamous Cell Carcinoma; D006801:Humans; D007527:Isoenzymes / Q000235:genetics*; D052119:Lysosomal-Associated Membrane Protein 2 / Q000235:genetics; D008869:Microtubule-Associated Proteins / Q000235:genetics; D011493:Protein Kinase C / Q000235:genetics*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D051176:beta Catenin / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D000099293:Protein Kinase C-lambda
D000071187:Autophagy-Related Protein 5; D007527:Isoenzymes; D052119:Lysosomal-Associated Membrane Protein 2; D008869:Microtubule-Associated Proteins; D011493:Protein Kinase C; D034741:RNA, Small Interfering; D051176:beta Catenin; D000099293:Protein Kinase C-lambda; C502778:ATG5 protein, human; C497811:LAMP2 protein, human
apoptosis; autophagic degradation; protein kinase Cι; β-catenin