Reciprocal interplay between asporin and decorin: Implications in gastric cancer prognosis

Authors

Dipjit Basak, Indian Statistical Institute, Kolkata
Zarqua Jamal, University of Calcutta
Arnab Ghosh, National Institute of Biomedical Genomics
Pronoy Kanti Mondal, Indian Statistical Institute, Kolkata
Priyanka Dey Talukdar, University of Calcutta
Semanti Ghosh, Saha Institute of Nuclear Physics
Biswadeep Ghosh Roy, Indian Statistical Institute, Kolkata
Ranajoy Ghosh, Institute of Post Graduate Medical Education and Research Kolkatta
Aniket Halder, Institute of Post Graduate Medical Education and Research Kolkatta
Abhijit Chowdhury, Institute of Post Graduate Medical Education and Research Kolkatta
Gopal Krishna Dhali, Institute of Post Graduate Medical Education and Research Kolkatta
Bitan Kumar Chattopadhyay, Institute of Post Graduate Medical Education and Research Kolkatta
Makhan Lal Saha, Institute of Post Graduate Medical Education and Research Kolkatta
Abhimanyu Basu, Institute of Post Graduate Medical Education and Research Kolkatta
Sukanta Roy, Institute of Post Graduate Medical Education and Research Kolkatta
Chitranjan Mukherjee, Delhi Technological University
Nidhan Kumar Biswas, National Institute of Biomedical Genomics
Urmi Chatterji, University of Calcutta
Shalini Datta, Indian Statistical Institute, Kolkata

Article Type

Research Article

Publication Title

PLoS ONE

Abstract

Effective patient prognosis necessitates identification of novel tumor promoting drivers of gastric cancer (GC) which contribute to worsened conditions by analysing TCGA-gastric adenocarcinoma dataset. Small leucine-rich proteoglycans, asporin (ASPN) and decorin (DCN), play overlapping roles in development and diseases; however, the mechanisms underlying their interplay remain elusive. Here, we investigated the complex interplay of asporin, decorin and their interaction with TGFβ in GC tumor and corresponding normal tissues. The mRNA levels, protein expressions and cellular localizations of ASPN and DCN were analyzed using real-time PCR, western blot and immunohistochemistry, respectively. The protein-protein interaction was predicted by in-silico interaction analysis and validated by co-immunoprecipitation assay. The correlations between ASPN and EMT proteins, VEGF and collagen were achieved using western blot analysis. A significant increase in expression of ASPN in tumor tissue vs. normal tissue was observed in both TCGA and our patient cohort. DCN, an effective inhibitor of the TGFβ pathway, was negatively correlated with stages of GC. Co-immunoprecipitation demonstrated that DCN binds with TGFβ, in normal gastric epithelium, whereas in GC, ASPN preferentially binds TGFβ. Possible activation of the canonical TGFβ pathway by phosphorylation of SMAD2 in tumor tissues suggests its role as an intracellular tumor promoter. Furthermore, tissues expressing ASPN showed unregulated EMT signalling. Our study uncovers ASPN as a GC-promoting gene and DCN as tumor suppressor, suggesting that ASPN can act as a prognostic marker in GC. For the first time, we describe the physical interaction of TGFβ with ASPN in GC and DCN with TGFβ in GC and normal gastric epithelium respectively. This study suggests that prevention of ASPN-TGFβ interaction or overexpression of DCN could serve as promising therapeutic strategies for GC patients. Copyright:

DOI

10.1371/journal.pone.0255915

Publication Date

8-1-2021

Comments

Open Access, Gold, Green

Recommended Citation

Basak, Dipjit; Jamal, Zarqua; Ghosh, Arnab; Mondal, Pronoy Kanti; Talukdar, Priyanka Dey; Ghosh, Semanti; Roy, Biswadeep Ghosh; Ghosh, Ranajoy; Halder, Aniket; Chowdhury, Abhijit; Dhali, Gopal Krishna; Chattopadhyay, Bitan Kumar; Saha, Makhan Lal; Basu, Abhimanyu; Roy, Sukanta; Mukherjee, Chitranjan; Biswas, Nidhan Kumar; Chatterji, Urmi; and Datta, Shalini, "Reciprocal interplay between asporin and decorin: Implications in gastric cancer prognosis" (2021). Journal Articles. 1850.
https://digitalcommons.isical.ac.in/journal-articles/1850