Smad Ubiquitination Regulatory Factor 1 (Smurf1) Promotes Thyroid Cancer Cell Proliferation and Migration via Ubiquitin-Dependent Degradation of Kisspeptin-1.
Yan. Chunyan C; Su. Haiying H; Song. Xiyuan X; Cao. Huiling H; Kong. Lingling L; Cui. Wen W
Key Findings
- Smurf1 is over‑expressed in thyroid tumor tissue and cancer cells
- Smurf1 tags kisspeptin‑1 for degradation via the ubiquitin‑proteasome system
- Increasing kisspeptin‑1 levels suppresses thyroid cancer cell growth and blocks NF‑κB signaling
Practical Outcomes
- For now, there’s no direct, safe way to use kisspeptin‑10 to improve health or longevity based on this work. The findings are mainly of interest for cancer research, and any attempt to boost kisspeptin without clinical trials could be ineffective or risky.
Summary
The study shows that a protein called Smurf1 is often higher in thyroid cancer cells and it helps break down another protein, kisspeptin‑1, which normally slows down cancer growth. When kisspeptin‑1 levels are increased, cancer cells grow less and die more, likely because it turns off a growth‑promoting pathway called NF‑κB. However, this research was done only in cell labs, not in people, so it doesn’t give clear guidance for health‑hacking or anti‑aging use.
Abstract
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.
Study Information
pubmed
2018
2018-09-21T00:00:00.000Z
10.1159/000493715
18
31