Invadopodia-Related Proteins Expression in Mucoepidermoid Carcinoma. A systematic review.

Dr. Karthik  Shunmugavelu; Dr. Niraimathi  Gnanasekaran

doi:10.51168/sjhrafrica.v4i6.2523

Authors

Dr. Karthik Shunmugavelu Assistant Professor, Department of Dentistry, PSP medical college hospital and research institute Tambaram Kanchipuram main road Oragadam Panruti Kanchipuram district Tamilnadu 631604 India.
Dr. Niraimathi Gnanasekaran Assistant professor, Department of Anesthesiology, PSP medical college hospital and research institute Tambaram Kanchipuram main road Oragadam Panruti Kanchipuram district Tamilnadu 631604 India.

DOI:

https://doi.org/10.51168/sjhrafrica.v4i6.2523

Keywords:

Mucoepidermoid carcinoma, Invadopodia, Tyrosine kinase substrate 4 (Tks4), Tyrosine kinase substrate 5 (Tks5), Cortactin, Membrane type 1 matrix metalloproteinase (MT1-MMP), Matrix metalloproteinase 2 (MMP-2), Matrix metalloproteinase 9 (MMP-9), Metallothionein

Abstract

Background

Mucoepidermoid carcinoma (MEC) is the most common malignant salivary gland tumor, displaying wide biological heterogeneity from indolent low-grade lesions to aggressive high-grade variants. Invadopodia are specialized actin-rich protrusions that degrade the extracellular matrix (ECM) and facilitate invasion. Core proteins such as Tks4, Tks5, cortactin and MT1-MMP, together with matrix metalloproteinases (MMP-2/9), have been implicated in invasion in several carcinomas, but their role in MEC has only recently been examined.

Objective: To systematically evaluate the expression of invadopodia-related proteins in MEC and their contribution to tumor invasiveness.

Methods

This review was conducted in accordance with PRISMA 2020 guidelines and the protocol was prospectively registered in PROSPERO (Registration ID: CRD420251152863). A comprehensive search of PubMed, Embase, Scopus and Web of Science was performed up to September 2025. Original studies analyzing invadopodia-related proteins in MEC were included. Data extraction covered study design, sample size, proteins evaluated, methodology and outcomes. Risk of bias was assessed using Joanna Briggs Institute (JBI) tools for tissue studies and an adapted appraisal framework for in vitro studies.

Results

Six studies met the inclusion criteria from 57 screened records. Immunohistochemistry demonstrated overexpression of Tks4, Tks5, cortactin and MT1-MMP in MEC compared with normal salivary glands. Functional silencing of Tks4/Tks5 reduced invadopodia formation, ECM degradation and cell invasiveness. MT1-MMP localized to carcinoma membranes and activated pro-MMP-2, while metallothionein enhanced invasiveness by modulating MMP-2/9. Clear-cell MEC also showed MMP-2 positivity on immunoarray analysis.

Conclusions

Invadopodia-related proteins are consistently expressed in MEC and appear to play a central role in its invasive phenotype. Larger multicenter studies with standardized protocols and integration of clinical outcomes are needed to establish their prognostic value and explore therapeutic potential.

Author Biographies

Dr. Karthik Shunmugavelu, Assistant Professor, Department of Dentistry, PSP medical college hospital and research institute Tambaram Kanchipuram main road Oragadam Panruti Kanchipuram district Tamilnadu 631604 India.

is an Oral and Maxillofacial Pathologist with multiple international fellowships and affiliations. He serves as Associate Faculty at the Faculty of Dental Trainers, Edinburgh and holds memberships with the Royal College of Surgeons of England and Glasgow. His research interests include salivary gland pathology, tumor invasion biology and systematic review methodology.

Dr. Niraimathi Gnanasekaran, Assistant professor, Department of Anesthesiology, PSP medical college hospital and research institute Tambaram Kanchipuram main road Oragadam Panruti Kanchipuram district Tamilnadu 631604 India.

is an Assistant Professor in the Department of Anaesthesiology at Srinivasan Medical College & Hospital, Trichy, India. She has expertise in perioperative medicine and contributes to collaborative research in head and neck oncology.

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