Lifestyle-associated hyperglycemia and aberrant TSH glycoforms in aggressive thyroid carcinoma: glycosylation-mediated mechanisms in treatment resistance hyperglycemia, TSH glycoforms & thyroid cancer
- 1Department of Biochemistry, Dr. Chandramma Dayananda Sagar Institute of Medical Education and Research, Dayananda Sagar University
- 2Department of Surgical Oncology, Dr. Chandramma Dayananda Sagar Institute of Medical Education and Research, Dayananda Sagar University
- 3Department of Pharmacology, College of Pharmaceutical Sciences, Dayananda Sagar University
Abstract
This review examines the critical intersection between lifestyle-associated hyperglycemia and aggressive thyroid carcinoma, with a particular focus on the role of aberrant thyroid-stimulating hormone (TSH) glycosylation. Chronic hyperglycemia, a characteristic of metabolic disorders such as type 2 diabetes, contributes to a pro-oxidative and pro-inflammatory tumor microenvironment. We propose that this metabolic stress enhances the hexosamine biosynthetic pathway, which may result in abnormal structural remodeling of TSH, specifically hypersialylation and increased N-glycan branching. We hypothesize that these altered TSH glycoforms dynamically interact with the TSH receptor. Due to their prolonged circulatory half-life, they may redirect canonical signaling toward sustained, atypical modulation of oncogenic networks, notably the PI3K/Akt/mTOR and MAPK pathways. These proposed signaling alterations could potentially contribute to tumor cell proliferation, epithelial-mesenchymal transition, immune evasion, and potential resistance to multimodal therapies in advanced thyroid carcinomas. These glycomic alterations may represent potential biomarker candidates; however, their diagnostic and prognostic utility remains clinically unvalidated. These findings provide a rationale for investigating whether metabolic regulation and glycosylation-targeted approaches could contribute to future strategies for overcoming treatment resistance in aggressive thyroid carcinomas.
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BibTeX
@article{p2026lifestyleassociated,
title = {{Lifestyle-associated hyperglycemia and aberrant TSH glycoforms in aggressive thyroid carcinoma: glycosylation-mediated mechanisms in treatment resistance hyperglycemia, TSH glycoforms & thyroid cancer}},
author = {Arya P. R. and Mehta Vedant Kamal and Kaushik Joshi and Chinmai Jagadish and Souwarna Jamadar and Prashant Tiwari},
journal = {Frontiers in Oncology},
year = {2026},
month = nov,
doi = {10.3389/fonc.2026.1968674},
url = {https://www.frontiersin.org/articles/10.3389/fonc.2026.1968674/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Lifestyle-associated hyperglycemia and aberrant TSH glycoforms in aggressive thyroid carcinoma: glycosylation-mediated mechanisms in treatment resistance hyperglycemia, TSH glycoforms & thyroid cancer
AU - Arya P. R.
AU - Mehta Vedant Kamal
AU - Kaushik Joshi
AU - Chinmai Jagadish
AU - Souwarna Jamadar
AU - Prashant Tiwari
PY - 2026
DA - 2026/11/09
JO - Frontiers in Oncology
DO - 10.3389/fonc.2026.1968674
UR - https://www.frontiersin.org/articles/10.3389/fonc.2026.1968674/full
AB - This review examines the critical intersection between lifestyle-associated hyperglycemia and aggressive thyroid carcinoma, with a particular focus on the role of aberrant thyroid-stimulating hormone (TSH) glycosylation. Chronic hyperglycemia, a characteristic of metabolic disorders such as type 2 diabetes, contributes to a pro-oxidative and pro-inflammatory tumor microenvironment. We propose that this metabolic stress enhances the hexosamine biosynthetic pathway, which may result in abnormal structural remodeling of TSH, specifically hypersialylation and increased N-glycan branching. We hypothesize that these altered TSH glycoforms dynamically interact with the TSH receptor. Due to their prolonged circulatory half-life, they may redirect canonical signaling toward sustained, atypical modulation of oncogenic networks, notably the PI3K/Akt/mTOR and MAPK pathways. These proposed signaling alterations could potentially contribute to tumor cell proliferation, epithelial-mesenchymal transition, immune evasion, and potential resistance to multimodal therapies in advanced thyroid carcinomas. These glycomic alterations may represent potential biomarker candidates; however, their diagnostic and prognostic utility remains clinically unvalidated. These findings provide a rationale for investigating whether metabolic regulation and glycosylation-targeted approaches could contribute to future strategies for overcoming treatment resistance in aggressive thyroid carcinomas.
SN - 2234-943X
ER -