evaluating-angiogenetic-properties-ovarian-cancer-stem-like-cells

Evaluating the Angiogenetic Properties of Ovarian Cancer Stem-Like Cells using the Three-Dimensional Co-Culture System, NICO-1

Cancer stem cells (CSCs) reside in a supportive niche, constituting a microenvironment comprised of adjacent stromal cells, vessels, and extracellular ...

Teikyo University School of Medicine

A previous report showed that a glucagon-like peptide-1 receptor (GLP-1R) agonist (exenatide) induced apoptosis in endometrial cancer cells. However, the pathophysiological role of GLP-1R in endometrial cancer has not been fully elucidated. Here, we investigated the effects of the GLP-1R agonist liraglutide in endometrial cancer cells and examined the association between GLP-1R expression and clinicopathological characteristics in endometrial cancer patients.

Expression of the glucagon-like peptide-1 receptor and its role in regulating autophagy in endometrial cancer.

Stratified mucin-producing intraepithelial lesion (SMILE) is a rare precursor lesion in the uterine cervix that is considered a variant of adenocarcinoma in situ (AIS). Although human papillomavirus (HPV) is thought to be related to the development of SMILE, there is little information available on the detection of HPV integrated into the lesion.

Detection of HPV RNA molecules in stratified mucin-producing intraepithelial lesion (SMILE) with concurrent cervical intraepithelial lesion: a case report.

The ubiquitin-proteasome pathway plays an important role in the regulation of cellular proteins. As an alternative to the proteasome itself, recent research has focused on methods to modulate the regulation of deubiquitinating enzymes (DUBs) upstream of the proteasome, identifying DUBs as novel therapeutic targets in breast, endometrial, and prostate cancers, along with multiple myeloma. bAP15, an inhibitor of the 19S proteasome DUBs UCHL5 and USP14, results in cell growth inhibition in several human cancers; however, the mechanism remains poorly understood in ovarian cancer. Here, we found that aberrant UCHL5 expression predicted shorter progression-free survival (PFS) in a cohort of 1435 patients with ovarian cancer described in the Gene Expression Omnibus and The Cancer Genome Atlas databases. The subgroup of patients with  mutations was significantly more likely to exhibit poor PFS ( <0.001). Moreover, we found bAP15 could suppress -mutant ovarian cancer cell survival by regulating TGF-β signaling through inhibiting UCHL5 expression and dephosphorylating Smad2, consequently inducing apoptosis. bAP15 (2.5 and 5.0 mg/kg) also exerted significant anti-tumor effect on nude mice bearing subcutaneous SKOV3 xenografts. As activated TGF-β signaling is involved in ovarian cancer progression, these findings suggest that UCHL5 inhibition offers potential opportunities for a novel targeted therapy against TGF-β-activated ovarian cancer.

Article	Year
Expression of the glucagon-like peptide-1 receptor and its role in regulating autophagy in endometrial cancer. BMC cancer\| PubMed ID: 29907137	2018
Detection of HPV RNA molecules in stratified mucin-producing intraepithelial lesion (SMILE) with concurrent cervical intraepithelial lesion: a case report. Virology journal\| PubMed ID: 31159808	2019
The proteasome deubiquitinase inhibitor bAP15 downregulates TGF-β/Smad signaling and induces apoptosis UCHL5 inhibition in ovarian cancer. Oncotarget\| PubMed ID: 31666925	2019

Takayuki Ichinose

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