Loss of WISP-2/CCN5 signaling in human pancreatic cancer: a potential mechanism for epithelial-mesenchymal-transition.
The objective of this study was to explore the pathophysiological relevance of WISP-2/CCN5 in progression of human pancreatic adenocarcinoma (PAC). We found WISP-2/CCN5 mRNA and protein expression was faint and sporadic in PAC and detected in only 8.7-20% of the samples with varying grades as compared to adjacent normal and chronic pancreatitis samples where expression was very high in the ducts and acini. Colocalization studies in tissue-microarray slides revealed WISP-2/CCN5 mRNA loss was associated with p53 overexpression in PAC. Like tissue samples, p53 mutant-PAC cell lines show loss of WISP-2/CCN5. Moreover, functional analysis studies demonstrate exposure of pancreatic cancer cells to WISP-2/CCN5 recombinant protein enhances mesenchymal-epithelial-transition (MET). Collectively, we suggest WISP-2/CCN5 silencing may be a critical event during differentiation and progression of PAC and mutant p53 is possibly an important player in pursuing this episode.
Dhar
Gopal
G
Cancer Research Unit, VA Medical Center, Kansas City, MO 64128, USA.
Mehta
Smita
S
Banerjee
Snigdha
S
Gardner
Ashleigh
A
McCarty
Bryan M
BM
Mathur
Sharad C
SC
Campbell
Donald R
DR
Kambhampati
Suman
S
Banerjee
Sushanta K
SK
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015152:Blotting, Northern; D015153:Blotting, Western; D055511:CCN Intercellular Signaling Proteins; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D045744:Cell Line, Tumor; D018450:Disease Progression; D004848:Epithelium / Q000378:metabolism / Q000473:pathology; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D008648:Mesoderm / Q000378:metabolism / Q000473:pathology; D010179:Pancreas / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D050500:Pancreatitis, Chronic / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology; D012097:Repressor Proteins; D015398:Signal Transduction / Q000235:genetics* / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
D055511:CCN Intercellular Signaling Proteins; C413323:CCN5 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D011994:Recombinant Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53