Knockdown of p62/sequestosome 1 attenuates autophagy and inhibits colorectal cancer cell growth

• Published in: Molecular and cellular biochemistry 2014-01, Vol.385 (1-2), p.95-102
• Main Authors: Ren, Feng, Shu, Guoshun, Liu, Ganglei, Liu, Dongcai, Zhou, Jiapeng, Yuan, Lianwen, Zhou, Jianping
• Format: Article
• Language: English
• Subjects: Adaptor Proteins, Signal Transducing - genetics; Adaptor Proteins, Signal Transducing - metabolism; Analysis; Animals; Autophagy; Autophagy - genetics; Biochemistry; Biomedical and Life Sciences; Biomedical research; Cardiology; Cell Line, Tumor; Cell Proliferation; Cellular signal transduction; Colorectal cancer; Colorectal carcinoma; Colorectal Neoplasms - genetics; Colorectal Neoplasms - pathology; Down-Regulation - genetics; Female; Gene Expression Regulation, Neoplastic; Gene Knockdown Techniques; Growth; Humans; Life Sciences; Male; Medical Biochemistry; Metastasis; Mice; Microtubule-Associated Proteins - metabolism; Middle Aged; Oncology; Sequestosome-1 Protein; Studies; Tumors; Up-Regulation - genetics
• ISSN: 0300-8177; 1573-4919
• DOI: 10.1007/s11010-013-1818-0

p62/sequestosome-1 is a multifunctional adapter protein implicated in selective autophagy, cell signaling pathways, and tumorigenesis, and plays an important role at the crossroad between autophagy and cancer. But, the connection between autophagy and cancer is complex and in some cases contradictory. Human colorectal cancer tissues from patients were analyzed for expression of p62 and Microtubule-associated protein light chain 3 (LC3, an autophagosome marker) using immunostaining, western blotting, real-time PCR, and confocal microscopy. To study the effects of p62 on autophagy and cell growth, shRNA for p62 was applied and cell growth curve was monitored in human colorectal cancer cell. In vivo experiments were done using the mouse xenograft model. We showed that up-regulated expression of p62 and LC3 in colorectal cancer tissues. We also demonstrated that specifically knockdown the expression of p62 showed significantly inhibitory effects not only on autophagy activation, but also on tumor growth both in vitro and xenograft tumors model. The ectopic overexpression of p62 and autophagy activation contributes to colorectal tumorigenesis. p62 and autophagy will be therapy targets for the treatment of colorectal cancer.