Hye-Yon Cho

The Role of ROR1 in Chemoresistance and EMT in Endometrial Cancer Cells

Background and Objectives: Receptor tyrosine kinase-like orphan receptor type 1 (ROR1) plays a critical role in embryogenesis and is overexpressed in many malignant cells. These characteristics allow ROR1 to be a potential new target for cancer treatment. The aim of this study was to investigate the role of ROR1 through in vitro experiments in endometrial cancer cell lines. Materials and Methods: ROR1 expression was identified in endometrial cancer cell lines using Western blot and RT-qPCR. The effects of ROR1 on cell proliferation, invasion, migration, and epithelial-mesenchymal transition (EMT) markers were analyzed in two endometrial cancer cell lines (HEC-1 and SNU-539) using either ROR1 silencing or overexpression. Additionally, chemoresistance was examined by identifying MDR1 expression and IC50 level of paclitaxel. Results: The ROR1 protein and mRNA were highly expressed in SNU-539 and HEC-1 cells. High ROR1 expression resulted in a significant increase in cell proliferation, migration, and invasion. It also resulted in a change of EMT markers expression, a decrease in E-cadherin expression, and an increase in Snail expression. Moreover, cells with ROR1 overexpression had a higher IC50 of paclitaxel and significantly increased MDR1 expression. Conclusions: These in vitro experiments showed that ROR1 is responsible for EMT and chemoresistance in endometrial cancer cell lines. Targeting ROR1 can inhibit cancer metastasis and may be a potential treatment method for patients with endometrial cancer who exhibit chemoresistance.

A Tissue Factor Bi-Specific T-Cell Engager Provides Effective Targeting and Cytotoxicity Against Cervical Cancer Cell Lines

Tissue factor (TF), also known as CD142, is a 47 kDa transmembrane glycoprotein belonging to the class II cytokine receptors superfamily. High expression of TF has been reported to be correlated with poor prognosis in various cancers. In this study, we aimed to clarify the cytotoxicity of bi-specific T-cell engagers (BiTE) targeting TF on cervical cancer cell lines. We designed and characterized the novel humanized BiTE targeting TF using an anti-human CD3 single-chain variable fragment (scFv) linked to human TF scFv. TF-Bite replication and potency were assessed in cervical cancer cell lines. The expression of the TF-BiTE and the activation and proliferation of T cells induced along with the T-cell-mediated cytotoxicity were evaluated by flow cytometry in vitro. TF expression was confirmed in SiHa, ME-180, and HeLa cell lines. The TF-BiTE showed potent TF-specific cytotoxicity and induced T-cell activation, proliferation, degranulation, and cytokine release. These effects were not observed in TF-negative control cells. Our findings support TF-BiTE as a promising therapeutic candidate for cervical cancer immunotherapy.

CT83 Promotes Cancer Progression by Upregulation of PDL1 in Adenocarcinoma of the Cervix

CT83, a cancer-testis antigen, has emerged as a potential biomarker and therapeutic target in various cancers. This study explores its expression and role in cervical adenocarcinoma progression and prognosis. CT83 expression was analyzed in cervical cancer cell lines using quantitative PCR and Western blotting. Functional assays demonstrated that CT83 overexpression (OE) promotes proliferation, migration, invasion, and epithelial–mesenchymal transition (EMT) in cervical cancer cells while also upregulating PD-L1 expression. Conversely, CT83 knockdown reduced these malignant phenotypes. The immunohistochemical analysis of 60 patient samples revealed CT83 expression in 84.9% of cases, with significant correlations to larger tumor size, elevated squamous cell carcinoma antigen (SCC) levels, and advanced FIGO stages (II–IV). Furthermore, intermediate-to-high CT83 expression (H-score ≥100) was associated with more aggressive disease features. These findings suggest that CT83 contributes to tumor progression and immune evasion, likely through PD-L1 modulation. As a highly expressed antigen in cervical adenocarcinoma, CT83 offers promise as a diagnostic marker and therapeutic target for improving patient outcomes.