Agrin is a novel oncogenic protein in thyroid cancer

Oncol Lett. 2023 Sep 25;26(5):483. doi: 10.3892/ol.2023.14070. eCollection 2023 Nov.

Abstract

Agrin (AGRN) is a matricellular glycoprotein involved in extracellular signal transduction. AGRN is involved in tumorigenesis and cancer progression; however, the role of AGRN in thyroid cancer (TC) remains unclear. In the present study, using cell lines derived from various subtypes of TC including CGTH, FTC-133 and BcPAP and transcriptomic data from patients with TC, the role of AGRN in TC was analyzed by migration, invasion, viability and proliferation assays as well as Western blot with EMT markers. AGRN expression was significantly increased in thyroid tumors and cell lines derived from various TC subtypes. The highest AGRN expression was found in follicular and papillary thyroid carcinoma subtypes. Immunocytochemistry revealed nuclear AGRN localization in normal (NTHY) and TC cells. Silencing of AGRN decreased viability, proliferation, migration and invasion of TC cell lines by upregulating vimentin and downregulating N-cadherin and E-cadherin. Furthermore, the expression of AGRN was associated with neutrophil infiltration in thyroid tumors. In conclusion, the present results indicated that increased AGRN expression promoted tumorigenic phenotypes of TC cells, while AGRN expression was associated with immune infiltration in thyroid tumors. AGRN may represent a target for future cancer therapy and requires further evaluation.

Keywords: agrin; invasion; migration; neutrophil infiltration; proliferation; thyroid cancer; viability.

Grants and funding

The present study was supported by The National Science Center, Poland (grant no. 2016/21/B/NZ5/00063) and The Centre of Postgraduate Medical Education, Poland (grant no. 501-1-025-01-23).