Dual role of the ELK3-CYFIP2 axis regulates actin dynamics and immune responses of triple-negative breast cancer during oncogenesis

---

Presentation Time: 11:30 AM - 12:45 PM
Poster Board Number: B969
Abstract ID: 7489

Presenting Author:
Seung Hee Choi , graduate student at CHA Univ.

Abstract:

During tumor progression and metastasis, certain cancer cells undergo epithelial-mesenchymal transition to detach from the primary tumor mass, which is protected by an immunosuppressive tumor microenvironment. Understanding the mechanisms through which metastatic tumor cells evade cytotoxic immune cells while circulating in the bloodstream is crucial for designing effective immunotherapeutics to prevent metastasis. In this study, we investigated the migration behavior and natural killer (NK) cell responses of genetically engineered triple negative breast cancer (TNBC) cell lines with suppressed ELK3 expression through shRNA. Our findings revealed a correlation between ELK3 expression level and filopodia protrusion from the cancer cell membrane, as well as actin accumulation at the contact site with NK cells. Gene expression profiling and molecular analysis demonstrated that ELK3 directly suppresses CYFIP2 expression, a component of the WAVE complex. Molecular and pharmacological analysis validated that the ELK3-CYFIP2 axis plays a dual role in TNBC cell lines: (1) regulating migration and adhesion via filopodia, and (2) influencing sensitivity to NK cells by regulating actin accumulation at the contact site. Taken together, the data strongly support the notion that targeting the ELK3-CYFIP2 axis could serve as a critical therapeutic strategy for eliminating metastatic cancer cells through NK cell-mediated immunotherapy.