ArticleBMC cancer2015
Mitogen-activated protein kinase activator with WD40 repeats (MAWD) and MAWD-binding protein induce cell differentiation in gastric cancer.
Article in BMC cancer, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers, 1 of them a synthesis that pooled it.
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Who cites it
6 citing papers in PubMed, 1 synthesis or guideline pooled it, 10 citations in OpenAlex.
- Gastric Cancer Associated Genes Identified by an Integrative Analysis of Gene Expression Data.BioMed research international · 2017Pooled it
- Epithelial PBLD attenuates intestinal inflammatory response and improves intestinal barrier function by inhibiting NF-κB signaling.Cell death & disease · 2021Article
- Novel compound cedrelone inhibits hepatocellular carcinoma progression via PBLD and Ras/Rap1.Experimental and therapeutic medicine · 2019Article
- circKDM4C suppresses tumor progression and attenuates doxorubicin resistance by regulating miR-548p/PBLD axis in breast cancer.Oncogene · 2019Article
- High Expression of long non-coding RNA PVT1 predicts metastasis in Han and Uygur Patients with Gastric Cancer in Xinjiang, China.Scientific reports · 2019Article
- Pepsinogen C expression, regulation and its relationship with cancer.Cancer cell international · 2017Review
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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.
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