Decorin impeded the advancement of thyroid papillary carcinoma by thwarting the EGFR/ FER/ SHP2 signaling-induced sustenance of early endosomes

Abstract

Objective: This study explores the inhibition of papillary thyroid carcinoma proliferation by Decorin via the EGFR/SHP2/FER pathway. Method: ology: Thirty-two pairs of papillary thyroid carcinoma tissues and adjacent normal tissues were collected for immunohistochemical analysis. Thyroid cancer cell lines with overexpressed or silenced Decorin were employed in subcutaneous tumor formation experiments in nude mice. Cell membrane proteins were extracted for Western blot and immunofluorescence analyses. Results: Reduced Decorin expression in human papillary thyroid carcinoma was associated with inhibited formation of the EGFR/SHP2/FER complex. Immunohistochemical analysis revealed lower Decorin levels in carcinoma tissues compared to adjacent normal tissues, corroborated by decreased Decorin and PTEN levels in carcinoma as shown by Western Blot. Overexpression of Decorin in mouse models diminished tumor growth, an effect reversed by Decorin silencing and mitigated by FER inhibition. Decorin modulated Rab5-GTP and Rab7-GTP levels, impacting endosome transition and subsequent signaling pathways. Conclusion: Decorin inhibits papillary thyroid carcinoma proliferation by disrupting the EGFR/SHP2/FER pathway and modulating endosomal transport.

Keywords

• Papillary thyroid carcinoma
• Decorin
• EGFR
• SHP2
• FER
• Endosomal transport