PKCα Activation via the Thyroid Hormone Membrane Receptor Is Key to Thyroid Cancer Growth.

Bibliographic Details
Title: PKCα Activation via the Thyroid Hormone Membrane Receptor Is Key to Thyroid Cancer Growth.
Authors: Campos Haedo, Mateo N.1 (AUTHOR) mateocamposhaedo@gmail.com, Díaz Albuja, Johanna A.1 (AUTHOR) johanna_diazalbuja@uca.edu.ar, Camarero, Sandra2 (AUTHOR) sandracamarero2@gmail.com, Cayrol, Florencia1 (AUTHOR) florencia_cayrol@uca.edu.ar, Sterle, Helena A.1 (AUTHOR) helena_sterle@uca.edu.ar, Debernardi, María M.1 (AUTHOR) mdebernardi@uca.edu.ar, Perona, Marina3,4 (AUTHOR) mperona@cnea.gov.ar, Saban, Melina5 (AUTHOR) msaban@hbritanico.com.ar, Ernst, Glenda6 (AUTHOR) GErnst@hbritanico.com.ar, Mendez, Julián7 (AUTHOR) jumendez@hbritanico.com.ar, Paulazo, María A.1 (AUTHOR) alejandra_paulazo@uca.edu.ar, Juvenal, Guillermo J.3,4 (AUTHOR) juvenal@cnea.gov.ar, Díaz Flaqué, María C.1 (AUTHOR) diazflaque@gmail.com, Cremaschi, Graciela A.1 (AUTHOR) graciela_cremaschi@uca.edu.ar, Rosemblit, Cinthia1 (AUTHOR) graciela_cremaschi@uca.edu.ar
Source: International Journal of Molecular Sciences. Nov2024, Vol. 25 Issue 22, p12158. 21p.
Subject Terms: *THYROID hormone receptors, *THYROID cancer, *TUMOR growth, *THYROID gland tumors, *IMMUNOHISTOCHEMISTRY
Abstract: Thyroid carcinoma (TC) is the most common endocrine neoplasia, with its incidence increasing in the last 40 years worldwide. The determination of genetic and/or protein markers for thyroid carcinoma could increase diagnostic precision. Accumulated evidence shows that Protein kinase C alpha (PKCα) contributes to tumorigenesis and therapy resistance in cancer. However, the role of PKCα in TC remains poorly studied. Our group and others have demonstrated that PKCs can mediate the proliferative effects of thyroid hormones (THs) through their membrane receptor, the integrin αvβ3, in several cancer types. We found that PKCα is overexpressed in TC cell lines, and it also appeared as the predominant expressed isoform in public databases of TC patients. PKCα-depleted cells significantly reduced THs-induced proliferation, mediated by the integrin αvβ3 receptor, through AKT and Erk activation. In databases of TC patients, higher PKCα expression was associated with lower overall survival. Further analyses showed a positive correlation between PKCα and genes from the MAPK and PI3K-Akt pathways. Finally, immunohistochemical analysis showed abnormal upregulation of PKCα in human thyroid tumors. Our findings establish a potential role for PKCα in the control of hormone-induced proliferation that can be explored as a therapeutic and/or diagnostic target for TC. [ABSTRACT FROM AUTHOR]
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ISSN:16616596
DOI:10.3390/ijms252212158
Published in:International Journal of Molecular Sciences
Language:English