kiss1-protein--human and Thyroid-Neoplasms

Thyroid cancer is the most common malignancy in human endocrine system. Smad ubiquitination regulatory factor 1 (Smurf1) is an E3 ubiquitin-protein ligase in ubiquitin-proteasome pathway (UPP) system. This study aimed to investigate the effects of Smurf1 on thyroid cancer proliferation and metastasis, as well as underlying potential mechanism.. The expression levels of Smurf1 in thyroid tumor tissues and thyroid cancer cells were detected by western blotting and qRT-PCR. Then, the effects of up-regulation or down-regulation of Smurf1 on thyroid cancer cell viability, migration, invasion, proliferation and apoptosis were measured using trypan blue exclusion assay, two-chamber migration (invasion) assay, cell colony formation assay and Guava Nexin assay, respectively. The ubiquitination of kisspeptin-1 (KISS-1) was assessed by protein ubiquitination assay. Finally, the effects of KISS-1 overexpression on activity of nuclear factor-kappa B (NF-κB) signaling pathway, as well as thyroid cancer cell viability, migration, invasion, proliferation and apoptosis were also detected, respectively.. Smurf1 was highly expressed in thyroid tumor tissues and thyroid cancer cells. Up-regulation of Smurf1 promoted the viability, migration, invasion and proliferation of thyroid cancer cells. Knockdown of Smurf1 had opposite effects. Moreover, smurf1 promoted the ubiquitination of KISS-1. Overexpression of KISS-1 inactivated NF-κB pathway, suppressed thyroid cancer cell viability, migration, invasion and proliferation, and induced cell apoptosis.. Up-regulation of Smurf1 exerted important roles in thyroid cancer formation and development by promoting thyroid cancer proliferation and metastasis. The ubiquitin-dependent degradation of KISS-1 induced by Smurf1 and the activation of NF-κB signaling pathway might be involved in this process. Smurf1 could be an effective therapy target and biomarker for thyroid cancer treatment.

Topics: Adult; Apoptosis; bcl-2-Associated X Protein; Caspase 3; Cell Line, Tumor; Cell Movement; Cell Proliferation; Female; Humans; Kisspeptins; Male; Middle Aged; NF-kappa B; RNA Interference; RNA, Small Interfering; Signal Transduction; Thyroid Neoplasms; Ubiquitin-Protein Ligases; Ubiquitination

KISS1 protein and KISS1 receptor form a system that mainly promotes suppression of metastasis in various forms of cancer. We studied the relationship between KISS1/KISS1R expression and tumor progression in differentiated thyroid cancer (DTC).. Thirty-three patients diagnosed with DTC were included in the study. Immunohistochemical cytoplasmic expression was evaluated for KISS1 and cytoplasmic/membranous expression for KISS1R in thyroid cancer tissues.. KISS1 expression was significantly higher in tumors with extrathyroidal invasion and advanced stage. KISS1R expression showed a statistically significant, moderate negative correlation with tumor size.. Increased expression of KISS1 is possibly acquired to prevent further tumor invasiveness and formation of local or distant metastasis. It appears that malignant cells in DTC express increased levels of KISS1 as the tumor invades extrathyroidal tissues. Decreased expression of KISS1R seems to attenuate signaling of the KISS1/KISS1R system, possibly leading to tumor growth.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Cell Differentiation; Cell Division; Female; Humans; Kisspeptins; Male; Middle Aged; Neoplasm Invasiveness; Receptors, G-Protein-Coupled; Receptors, Kisspeptin-1; Thyroid Neoplasms; Young Adult

Tumor metastasis is a critical determinant of death from cancer. Metastin, a product of the KiSS-1 gene, is an endogenously expressed metastasis suppressor that is the ligand for G protein-coupled receptor 54 (GPR54), a Gq/11-coupled receptor. In the present study, our goal was to define the basis of GPR54 action using thyroid cancer cells as a model.. We used GPR54-null thyroid cancer cells to create a stable GPR54 overexpression model. Cell growth and cell migration of the GPR54-expressing lines were inhibited by recombinant metastin, and metastin stimulated the protein kinase C, ERK, and phosphatidylinositol-3-kinase pathways. To identify metastin-regulated genes, we performed microarray analyses using RNA isolated from GPR54 stable transfectants before and after 1 and 24 h of metastin stimulation. Consistent increases in expression of the gene encoding myocyte-enriched calcineurin interacting protein 1 (MCIP-1), an inhibitor of calcineurin, were identified and confirmed using real-time RT-PCR and Western blot. Functionally, metastin treatment of GPR54-expressing cells initially increased calcineurin activity, followed by a prolonged reduction in calcineurin activity for 24 and 48 h, consistent with the pattern of MCIP-1 expression. In addition, treatment with cyclosporin A, a calcineurin inhibitor, blocked cell migration. Lymph node metastasis in papillary thyroid cancers demonstrated loss of MCIP-1 expression in comparison with primary tumors.. These data suggest a role for MCIP-1 and calcineurin inhibition in GPR54-mediated metastasis suppression in human cancers.

Topics: Calcineurin Inhibitors; Cell Division; Cell Line, Tumor; Cell Movement; DNA-Binding Proteins; Extracellular Signal-Regulated MAP Kinases; Gene Expression Regulation, Neoplastic; Humans; Intracellular Signaling Peptides and Proteins; Kisspeptins; Muscle Proteins; Neoplasm Metastasis; Oligonucleotide Array Sequence Analysis; Phosphorylation; Protein Kinase C; Protein Serine-Threonine Kinases; Proteins; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-akt; Receptors, G-Protein-Coupled; Receptors, Kisspeptin-1; Receptors, Neuropeptide; Thyroid Neoplasms; Time Factors; Tumor Suppressor Proteins; Up-Regulation