Paradoxical role of CBX8 in proliferation and metastasis of colorectal cancer
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Jianjun Tang1,*, Gang Wang1,*, Meifang Zhang1,*, Feng-yan Li1, Yi Sang1, Boqing Wang1,2, Kaishun Hu1, Yuanzhong Wu1, Rongzhen Luo1, Dan Liao1, Jingying Cao1, Xin Wang1, Li Wang1, Ruhua Zhang1, Xiaoshi Zhang1, Wu-Guo Deng1, Dan Xie1, Rui-hua Xu1, Tiebang Kang1
1State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou 510060, China
2 Department of Hepatobiliarypancreatic Surgery, Affiliated Tumor Hospital, Xinjiang Medical University, Urumqi 830000, China
*These authors contributed equally to this work
Tiebang Kang, e-mail: [email protected]
Keywords: CBX8, Polycomb Group protein, colorectal cancer, metastasis, proliferation, p53, integrin
Received: July 23, 2014 Accepted: September 13, 2014 Published: October 24, 2014
The effect of polycomb chromobox (Cbx) proteins in cancer is context-dependent. The Chromobox homolog 8 (CBX8) was originally characterized as a transcriptional repressor, which inhibits cell proliferation in Ink4a-Arf-dependent and -independent manner. However, the role of CBX8 in colorectal cancer remains unknown. Here, we found that high CBX8 expression was associated with a low rate of distant metastasis and good prognosis in CRC patients, even though CBX8 was up-regulated in CRC cell lines and clinical samples. Knockdown of CBX8 inhibited CRC proliferation in vitro and in vivo, mostly by increasing p53 and its downstream effectors. However, knockdown of CBX8 enhanced CRC migration, invasion and metastasis in vitro and in vivo, in part through direct up-regulation of integrin β4 (ITGB4) that in turn decreased RhoA activity. Collectively, the knockdown of CBX8 inhibited CRC proliferation, while promoting its metastasis, thus exerting paradoxical effects in CRC progression.
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