Mitogen-activated protein kinase activator with WD40 repeats (MAWD) and MAWD-binding protein induce cell differentiation in gastric cancer

BMC Cancer

Research Article

Dongmei Li¹  Zemin Pan¹  Feng Li¹  Yu Xi²  Lei Zhang³  Wenmei Li⁴  Jiantao Cui⁴  Youyong Lu⁴  Rui Xing⁴  Yuanmin Pan⁴  Jun Zhang⁵ 

[1] Department of Biochemistry and Molecular Biology, School of Medicine, Shihezi University, 832000, Xinjiang, P.R. China;Department of General Surgery, First Affiliated Hospital of Shihezi University, 832008, Shihezi, Xinjiang, P.R. China;Department of Laboratory, First Affiliated Hospital of Shihezi University, 832008 P.R, Shihezi, Xinjiang, China;Laboratory of Molecular Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital/Institute, 100142, Beijing, P.R. China;Laboratory of Molecular Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital/Institute, 100142, Beijing, P.R. China;Beijing Genomics Institute, Chinese Academy of Sciences, 101318, Shunyi, Beijing, P.R. China;

关键词: Gastric Cancer;    Gastric Cancer Cell;    Gastric Cancer Tissue;    SGC7901 Cell;    Vector Group;   

DOI  :  10.1186/s12885-015-1637-7

 received in 2014-12-08, accepted in 2015-09-01,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundOur previous proteomic analysis revealed that mitogen-activated protein kinase activator with WD40 repeats (MAWD) and MAWD-binding protein (MAWBP) were downregulated in gastric cancer (GC) tissues. These proteins interacted and formed complexes in GC cells. To investigate the role of MAWD and MAWBP in GC differentiation, we analyzed the relationship between MAWD/MAWBP and clinicopathologic characteristics of GC tissues and examined the expression of E-cadherin and pepsinogen C (PGC)—used as gastric mucosa differentiation markers—in MAWD/MAWBP-overexpressing GC cells and xenografts.MethodsWe measured MAWD, MAWBP, transforming growth factor-beta (TGF-beta), E-cadherin, and PGC expression in 223 GC tissues and matched-adjacent normal tissues using tissue microarray and immunohistochemistry (IHC) analyses, and correlated these expression levels with clinicopathologic features. MAWD and MAWBP were overexpressed alone or together in SGC7901 cells and then E-cadherin, N-cadherin, PGC, Snail, and p-Smad2 levels were determined using western blotting, semiquantitative RT-PCR, and immunofluorescence analysis. Alkaline phosphatase (AKP) activity was measured to investigate the differentiation level of various transfected cells, and the transfected cells were used in tumorigenicity assays and for IHC analysis of protein expression in xenografts.ResultsMAWD/MAWBP positive staining was significantly lower in GC tissues than in normal samples (P < 0.001), and the expression of these proteins was closely correlated with GC differentiation grade. Kaplan–Meier survival curves indicated that low MAWD and MAWBP expression was associated with poor patient survival (P < 0.05). The differentiation-related proteins E-cadherin and PGC were expressed in GC tissues at a lower level than in normal tissues (P < 0.001), but were upregulated in MAWD/MAWBP-overexpressing cells. N-cadherin and Snail expression was strongr in vector-expressing cells and comparatively weaker in MAWD/MAWBP co-overexpressing cells. MAWD/MAWBP co-overexpression inhibited Smad2 phosphorylation and nuclear translocation (P < 0.05), and AKP activity was lowest in MAWD/MAWBP coexpressing cells and highest in vector-expressing cells (P < 0.001). TGF-beta, E-cadherin, and PGC expression in xenograft tumors derived from MAWD/MAWBP coexpressing cells was higher than that in control.ConclusionsMAWD and MAWBP were downregulated and associated with the differentiation grade in GC tissues. MAWD and MAWBP might induce the expression of differentiation-related proteins by modulating TGF-beta signaling in GC cells.

【 授权许可】

CC BY   
© Li et al. 2015