Looking at Thyroid Cancer from the Tumor-Suppressor Genes Point of View.

Thyroid cancer is the most frequent endocrine malignancy and accounts for approximately 1% of all diagnosed cancers. A variety of mechanisms are involved in the transformation of a normal tissue into a malignant one. Loss of tumor-suppressor gene (TSG) function is one of these mechanisms. The normal functions of TSGs include cell proliferation and differentiation control, genomic integrity maintenance, DNA damage repair, and signaling pathway regulation. TSGs are generally classified into three subclasses: (i) gatekeepers that encode proteins involved in cell cycle and apoptosis control; (ii) caretakers that produce proteins implicated in the genomic stability maintenance; and (iii) landscapers that, when mutated, create a suitable environment for malignant cell growth. Several possible mechanisms have been implicated in TSG inactivation. Reviewing the various TSG alteration types detected in thyroid cancers may help researchers to better understand the TSG defects implicated in the development/progression of this cancer type and to find potential targets for prognostic, predictive, diagnostic, and therapeutic purposes. Hence, the main purposes of this review article are to describe the various TSG inactivation mechanisms and alterations in human thyroid cancer, and the current therapeutic options for targeting TSGs in thyroid cancer.

Metastatic propagation of thyroid cancer; organ tropism and major modulators.

Thyroid cancer, as the most prevalent endocrine malignancy, comprises nearly 1% of all cancers in the world. The metastatic propagation of thyroid cancer is under the control of a number of modulating processes and factors such as signaling pathways and their components, cell division regulators, metabolic reprogramming factors, extracellular matrix remodelers, epithelial to mesenchymal transition modulators, epigenetic mechanisms, hypoxia and cytokines. Identifying the exact molecular mechanisms of these dysregulated processes could help to discover the key targets for therapeutic purposes and utilizing them as diagnostic, prognostic and predictors of the clinical course of patients. In this review article, we describe different aspects of thyroid cancer metastasis by focusing on defective genes and pathways involved in its metastatic spread.

Epithelial-to-mesenchymal transition in thyroid cancer: a comprehensive review.

The Metastatic progression of solid tumors, such as thyroid cancer is a complex process which involves various factors. Current understanding on the role of epithelial-mesenchymal transition (EMT) in thyroid carcinomas suggests that EMT is implicated in the progression from follicular thyroid cancer (FTC) and papillary thyroid cancer (PTC) to poorly differentiated thyroid carcinoma (PDTC) and anaplastic thyroid cancer (ATC). According to the literature, the initiation of the EMT program in thyroid epithelial cells elevates the number of stem cells, which contribute to recurrent and metastatic diseases. The EMT process is orchestrated by a complex network of transcription factors, growth factors, signaling cascades, epigenetic modulations, and the tumor milieu. These factors have been shown to be dysregulated in thyroid carcinomas. Therefore, molecular interferences restoring the expression of tumor suppressors, or thwarting overexpressed oncogenes is a hopeful therapeutic method to improve the treatment of progressive diseases. In this review, we summarize the recent findings on EMT in thyroid cancer focusing on the main role-players and regulators of this process in thyroid tumors.