BRAF-Oncogene-Induced Senescence and the Role of Thyroid-Stimulating Hormone Signaling in the Progression of Papillary Thyroid Carcinoma

Oncogene-induced senescence (OIS) explains the phenomenon of cellular senescence triggered by the action of oncogenes. It is a mechanism adopted by a cell to inhibit progression of benign tumors into malignancy, occurs in premalignant lesions, and is almost never present in malignant lesions. BRAF m...

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Published in:	Hormones & cancer Vol. 9; no. 1; pp. 1 - 11
Main Authors:	Moulana, F. I., Priyani, A. A. H., de Silva, M. V. C., Dassanayake, R. S.
Format:	Journal Article
Language:	English
Published:	New York Springer US 01-02-2018
Subjects:	Cell Biology Cellular Senescence - genetics Disease Progression Dual Specificity Phosphatase 6 - genetics Endocrinology Humans Internal Medicine Medicine Medicine & Public Health Microbiology Mutation Oncology Proto-Oncogene Proteins B-raf - genetics Proto-Oncogene Proteins c-myc - genetics Receptors, G-Protein-Coupled - genetics Review Signal Transduction - genetics Superoxide Dismutase - genetics Systems Biology Thyroid Cancer, Papillary - genetics Thyroid Cancer, Papillary - pathology Thyrotropin - genetics Dual Specificity Phosphatase (DUSP6) Papillary Thyroid Carcinomas (PTC) Manganese Superoxide Dismutase (MnSOD) BRAFV600E Mutation Thyroid-stimulating Hormone Receptor (TSHR)
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Summary:	Oncogene-induced senescence (OIS) explains the phenomenon of cellular senescence triggered by the action of oncogenes. It is a mechanism adopted by a cell to inhibit progression of benign tumors into malignancy, occurs in premalignant lesions, and is almost never present in malignant lesions. BRAF mutations occur in about 40–45% of all papillary thyroid carcinomas (PTCs) and of which 99.7% is the BRAF V600E mutation. A unique phenotype of the BRAF V600E mutation is the upregulation of the thyroid-stimulating hormone receptor (TSHR) on thyrocyte membranes. Despite the overexpression of the receptor, BRAF V600E cells undergo cell cycle arrest leading to OIS via a negative feedback signaling mechanism. A simultaneous increase in serum thyroid-stimulating hormone (TSH) in response to hypothyroidism (common in autoimmune diseases such as Hashimoto’s thyroiditis) would cause senescent tumor cells to overcome OIS and proceed towards malignancy, hence showing the importance of TSH/TSHR signaling in the development of PTCs. Increase in TSH/TSHR signaling triggers an increase in levels of downstream enzymes such as manganese superoxide dismutase (MnSOD) and dual-specific phosphatase 6 (DUSP6) which eventually results in the production of oncogenic proteins such as c-Myc. Therefore, the detection of these genetic alterations as effective biomarkers for premalignant lesions of PTC is important in clinical settings and techniques such as polymerase chain reaction-mediated restriction fragment length polymorphism (PCR-RFLP) and real-time PCR can be used to detect the BRAF V600E point mutation and overexpression of TSHR , MnSOD , and DUSP6 , respectively.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-3 content type line 23 ObjectType-Review-1
ISSN:	1868-8497 1868-8500
DOI:	10.1007/s12672-017-0315-4