HOXB7 overexpression promotes cell proliferation and correlates with poor prognosis in gastric cancer patients by inducing expression of both AKT and MARKs

// Xujun He 1 , Zhengchuang Liu 1 , Yingjie Xia 1 , Ji Xu 1, 2 , Guocai Lv 3, 4 , Lu Wang 1 , Tonghui Ma 1 , Liping Jiang 1 , Yiping Mou 1, 2 , Xiaoting Jiang 1 , Jie Ma 5, 6 , Zhongkuo Zhao 1, 2 , Haibin Ni 7 , Wenjuan Xu 5, 6 , Guoqing Ru 5, 6 , Dongsheng Huang 2 , Houquan Tao 1, 2 1 Key Laboratory of Gastroenterology of Zhejiang Province, Hangzhou, 310014, China 2 Department of Surgery, Zhejiang Provincial People’s Hospital, Hangzhou 310014, Zhejiang, China 3 Department of Laboratory Medicine, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China 4 Key Laboratory of Clinical In vitro Diagnostic Techniques of Zhejiang Province, Hangzhou 310003, China 5 Department of Pathology, Zhejiang Provincial People’s Hospital, Hangzhou 310014, Zhejiang, China 6 Department of Cardiothoracic Surgery, Zhejiang Provincial People’s Hospital, Hangzhou 310014, Zhejiang, China 7 Department of Surgery, Tongde Hospital of Zhejiang Province, Hangzhou 310012, Zhejiang, China Correspondence to: Houquan Tao, email: taohouquan2008@aliyun.com Keywords: HOXB7, gastric cancer, prognosis, AKT, MAPKs Received: March 14, 2016      Accepted: November 11, 2016      Published: November 25, 2016 ABSTRACT Increased expression of HOXB7 has been reported to correlate with the progression in many cancers. However, the specific mechanism by which it promotes the evolution of gastric cancer (GC) is poorly understood. In this study, we sought to investigate the role of HOXB7 in GC by assessing HOXB7 expression in patient tissue and its correlation to clinical characteristics. We found that GC tissues showed increased expression of HOXB7 and that the HOXB7 expression was significantly associated with Lauren classification, invasion depth, lymphatic metastasis and poor prognosis, and could serve as an independent prognostic factor. To further investigate the role of HOXB7 in GC, we generated stable GC cell lines and both over-expressed and knocked down HOXB7 expression. Over-expression of HOXB7 in GC cell lines enhanced cell proliferation, colony formation, migration and invasion ability, whereas the opposite trends were observed upon reduction of HOXB7 expression by knockdown. These findings were further supported by our in vivo studies which show that HOXB7 expression can affect the GC cells’ subcutaneous growth and lung metastases. A Phospho-MAPK Array Kit was used to explore the possible mechanism of HOXB7-induced cell proliferation and invasion. We found that the AKT signaling pathway and the two members of the MAPK pathway, were involved in those promoting effects. In conclusion, our results showed that increased expression of HOXB7 might play an important role in promoting GC proliferation, migration and invasion by inducing both AKT and MAPK pathways, thus resulting in progression of, and poor prognosis in GC patients.