title: HOXB7 overexpression promotes cell proliferation and correlates with poor prognosis in gastric cancer patients by inducing expression of both AKT and MARKs.
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.
authors.affiliation: Key Laboratory of Gastroenterology of Zhejiang Province, Hangzhou, 310014, China.
authors.forename: Xujun
authors.initials: X
authors.lastname: He
authors.affiliation: Key Laboratory of Gastroenterology of Zhejiang Province, Hangzhou, 310014, China.
authors.forename: Zhengchuang
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Key Laboratory of Gastroenterology of Zhejiang Province, Hangzhou, 310014, China.
authors.forename: Yingjie
authors.initials: Y
authors.lastname: Xia
authors.affiliation: Key Laboratory of Gastroenterology of Zhejiang Province, Hangzhou, 310014, China.|Department of Surgery, Zhejiang Provincial People's Hospital, Hangzhou 310014, Zhejiang, China.
authors.forename: Ji
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Laboratory Medicine, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China.|Key Laboratory of Clinical In vitro Diagnostic Techniques of Zhejiang Province, Hangzhou 310003, China.
authors.forename: Guocai
authors.initials: G
authors.lastname: Lv
authors.affiliation: Key Laboratory of Gastroenterology of Zhejiang Province, Hangzhou, 310014, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Wang
authors.affiliation: Key Laboratory of Gastroenterology of Zhejiang Province, Hangzhou, 310014, China.
authors.forename: Tonghui
authors.initials: T
authors.lastname: Ma
authors.affiliation: Key Laboratory of Gastroenterology of Zhejiang Province, Hangzhou, 310014, China.
authors.forename: Liping
authors.initials: L
authors.lastname: Jiang
authors.affiliation: Key Laboratory of Gastroenterology of Zhejiang Province, Hangzhou, 310014, China.|Department of Surgery, Zhejiang Provincial People's Hospital, Hangzhou 310014, Zhejiang, China.
authors.forename: Yiping
authors.initials: Y
authors.lastname: Mou
authors.affiliation: Key Laboratory of Gastroenterology of Zhejiang Province, Hangzhou, 310014, China.
authors.forename: Xiaoting
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Department of Pathology, Zhejiang Provincial People's Hospital, Hangzhou 310014, Zhejiang, China.|Department of Cardiothoracic Surgery, Zhejiang Provincial People's Hospital, Hangzhou 310014, Zhejiang, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Ma
authors.affiliation: Key Laboratory of Gastroenterology of Zhejiang Province, Hangzhou, 310014, China.|Department of Surgery, Zhejiang Provincial People's Hospital, Hangzhou 310014, Zhejiang, China.
authors.forename: Zhongkuo
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: Department of Surgery, Tongde Hospital of Zhejiang Province, Hangzhou 310012, Zhejiang, China.
authors.forename: Haibin
authors.initials: H
authors.lastname: Ni
authors.affiliation: Department of Pathology, Zhejiang Provincial People's Hospital, Hangzhou 310014, Zhejiang, China.|Department of Cardiothoracic Surgery, Zhejiang Provincial People's Hospital, Hangzhou 310014, Zhejiang, China.
authors.forename: Wenjuan
authors.initials: W
authors.lastname: Xu
authors.affiliation: Department of Pathology, Zhejiang Provincial People's Hospital, Hangzhou 310014, Zhejiang, China.|Department of Cardiothoracic Surgery, Zhejiang Provincial People's Hospital, Hangzhou 310014, Zhejiang, China.
authors.forename: Guoqing
authors.initials: G
authors.lastname: Ru
authors.affiliation: Department of Surgery, Zhejiang Provincial People's Hospital, Hangzhou 310014, Zhejiang, China.
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Huang
authors.affiliation: Key Laboratory of Gastroenterology of Zhejiang Province, Hangzhou, 310014, China.|Department of Surgery, Zhejiang Provincial People's Hospital, Hangzhou 310014, Zhejiang, China.
authors.forename: Houquan
authors.initials: H
authors.lastname: Tao
mesh_terms: D000368:Aged; D000818:Animals; D014408:Biomarkers, Tumor; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D064593:Heterografts; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics* / Q000378:metabolism; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011379:Prognosis; D016016:Proportional Hazards Models; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality* / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; C490538:HOXB7 protein, human; D018398:Homeodomain Proteins; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases
keywords: AKT; HOXB7; MAPKs; gastric cancer; prognosis