Protein Expression Analysis and Functional Characterization of Sorcin in Gallbladder Cancer
Vaishali Jain1,2, Neeraj Saklani1,2, Srishti Kawatra1,2
1ICMR-Centre for Cancer Pathology (Formerly a Part of ICMR-National Institute of Pathology), Safdarjung Hospital Campus, New Delhi 110029, India.
Abstract:
Gallbladder cancer (GBC) is an aggressive malignancy with limited treatment options and poor clinical outcomes. Identifying novel molecular targets is critical for improving therapeutic strategies. Sorcin (SRI), a calcium-binding protein implicated in tumor progression, has not been comprehensively investigated in GBC. SRI expression was analyzed by immunohistochemistry (IHC) in a large cohort of gallstone disease (GSD) controls (n = 85) and GBC tissues (n = 85). Functional assays, including cell proliferation, wound healing, transwell invasion, and Western blot analyses of epithelial-mesenchymal transition (EMT) markers, were performed in the NOZ GBC cell line following siRNA-mediated SRI knockdown. IHC revealed that 67% of GBC cases exhibited positive staining whereas all the GSD cases exhibited negative staining of SRI, demonstrating a significant upregulation of SRI in GBC (p < 0.001). SRI knockdown resulted in reduced proliferative capacity and markedly impaired migration and invasion. Further, SRI knockdown decreased vimentin levels, indicating suppression of EMT. SRI is significantly overexpressed in GBC and promotes key oncogenic traits, including proliferation, migration, invasion, and EMT. These findings highlight SRI as a potential therapeutic target in GBC. Further validation in animal models may facilitate translation into clinical applications.
Insights
Sorcin (SRI) is significantly upregulated in gallbladder cancer (GBC) and promotes tumor growth and spread. Targeting SRI may offer a new therapeutic strategy for GBC patients.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Gallbladder cancer (GBC) is an aggressive malignancy with poor outcomes.
- Novel molecular targets are crucial for developing effective GBC therapies.
- Sorcin (SRI), a calcium-binding protein, has a known role in tumor progression but its role in GBC is understudied.
Purpose of the Study:
- To investigate the expression of Sorcin (SRI) in GBC tissues.
- To determine the functional role of SRI in GBC cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT).
Main Methods:
- Immunohistochemistry (IHC) was used to analyze SRI expression in 85 GBC tissues and 85 gallstone disease (GSD) controls.
- siRNA-mediated SRI knockdown was performed in the NOZ GBC cell line.
- Functional assays included cell proliferation, wound healing, transwell invasion, and Western blot analysis of EMT markers.
Main Results:
- SRI was significantly upregulated in 67% of GBC cases compared to negative staining in all GSD controls (p < 0.001).
- SRI knockdown reduced GBC cell proliferation, migration, and invasion.
- SRI knockdown suppressed vimentin expression, indicating inhibition of EMT.
Conclusions:
- SRI is significantly overexpressed in GBC and promotes key oncogenic behaviors.
- SRI is a potential therapeutic target for GBC.
- Further studies in animal models are warranted for clinical translation.
