Paradoxical role of CBX8 in proliferation and metastasis of colorectal cancer

// Jianjun Tang 1, * , Gang Wang 1, * , Meifang Zhang 1, * , Feng-yan Li 1 , Yi Sang 1 , Boqing Wang 1, 2 , Kaishun Hu 1 , Yuanzhong Wu 1 , Rongzhen Luo 1 , Dan Liao 1 , Jingying Cao 1 , Xin Wang 1 , Li Wang 1 , Ruhua Zhang 1 , Xiaoshi Zhang 1 , Wu-Guo Deng 1 , Dan Xie 1 , Rui-hua Xu 1 , Tiebang Kang 1 1 State 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 Correspondence to: Tiebang Kang, e-mail: kangtb@mail.sysu.edu.cn Keywords: CBX8, Polycomb Group protein, colorectal cancer, metastasis, proliferation, p53, integrin Received: July 23, 2014      Accepted: September 13, 2014      Published: October 24, 2014 ABSTRACT 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.