한빛사
>
한빛사논문
한빛사논문
- 조회310
J. Exp. Clin. Cancer Res., Feb 10 2025, 44 (1) | https://doi.org/10.1186/s13046-025-03309-7
ELK3-CYFIP2 axis-mediated actin remodeling modulates metastasis and natural killer cell responses in triple-negative breast cancer
Seung Hee Choi1, Hye Jung Jang2, Joo Dong Park2, Ki Seo Ryu1, Eunchong Maeng1, Seohyun Cho1, Hail Park1, Hae‑Yun Jung3 and Kyung‑Soon Park1*
1Department of Biomedical Science, CHA University, Seongnam, Republic of Korea
2Department of Integrative Biotechnology, Sungkyunkwan University, Suwon, Republic of Korea
3Division of Radiation Biomedical Research, Korea Institute of Radiological and Medical Sciences, Seoul, Republic of Korea
*Correspondence: Kyung‑Soon Park
1Department of Biomedical Science, CHA University, Seongnam, Republic of Korea
2Department of Integrative Biotechnology, Sungkyunkwan University, Suwon, Republic of Korea
3Division of Radiation Biomedical Research, Korea Institute of Radiological and Medical Sciences, Seoul, Republic of Korea
*Correspondence: Kyung‑Soon Park
Abstract
Triple-negative breast cancer (TNBC) is an aggressive, highly metastatic disease with a poor prognosis. E26 transformation-specific transcription factor (ELK3) is highly expressed in TNBCs, and functions as a regulator of epithelial-mesenchymal transition and immune responses. Because metastatic migration and immune evasion by TNBC cells are critical factors for successful metastasis, unravelling the underlying mechanisms and developing effective immunotherapeutic strategies is urgent. Here, TNBC cell lines MDA-MB-231 and Hs578T were examined to determine the relationship between ELK3 expression and filopodia protrusion on the cell membrane, as well as actin accumulation at contact sites with natural killer (NK) cells. RNA-sequencing analysis and molecular experiments were conducted to identify and validate downstream target genes of ELK3 associated with migration and attachment of TNBC cells. The immune response of TNBC to NK cells was evaluated through imaging and flow cytometry analyses. Clinical significance was assessed through Kaplan-Meier analysis of survival outcomes of TNBC patients. Gene expression profiling and molecular analysis revealed that oncogenic ELK3 directly suppresses expression of cytoplasmic FMR1 interacting protein2 (CYFIP2), a repressor of actin accumulation. Further molecular and pharmacological analyses confirmed that the ELK3-CYFIP2 axis serves a dual role in TNBC cell lines by (1) controlling filopodia-mediated migration and adhesion by regulating actin accumulation, and (2) regulating sensitivity to NK cells by modulating actin accumulation at contact sites. Kaplan-Meier analysis suggested that ELK3-CYFIP2 axis is associated with survival of TNBC patients, and that ELK3 suppresses transcription of CYFIP2. Thus, the ELK3-CYFIP2 axis plays a pivotal role in regulating actin, emphasizing its significance in controlling both cancer cell migration and NK cell responses in TNBC.
논문정보
- Research article
- 2025년 02월 (BRIC 등록일 2025-02-18)
- 국내 연구진
- 생명과학 > 면역학
관련 웨비나
![삼중음성 유방암에서 ELK3-CYFIP2 축 매개 actin 역학의 전이 및 자연살해세포 반응 조절 기전 연구 [J. Exp. Clin. Cancer Res.]](/upload/board/files/onseminar/thumb/thumb_0000906.png)
학술웨비나
삼중음성 유방암에서 ELK3-CYFIP2 축 매개 actin 역학의 전이 및 자연살해세포 반응 조절 기전 연구 [J. Exp. Clin. Cancer Res.] 삼중음성유방암(Triple-negative breast cancer, TNBC)는 전이성이 높고 예후가 좋지않은 질환입니다. ELK3(E26 transformation-specific transcription factor)는 TNBC에서 높게 발현되며, 상피-중간엽 전이 (EMT) 및 자연살해세포(Natural killer, NK) 매개 면역반응의 조절자로 기능합니다. 본 연구에서는 ELK3 발현이 세포막의 필로포디아 돌출부 및 자연 살해(NK)세포와의 접촉 부위에서의 actin 축적과 상관관계를 갖는다는 것을 발견하였습니다. 또한, ELK3의 하류 표적 유전자를 식별하고 및 프로파일링하는 과정에서 ELK3가 CYFIP2 (cytoplasmic FMR1 interacting protein2)의 발현을 직접 억제하는 것을 증명하였습니다. 따라서, ELK3-CYFIP2 축이 actin 축적을 조절하여 (1) TNBC의 전이를 촉진하는 동시에 (2) NK세포와의 접촉을 방해하여 면역회피를 유도한다는 것을 규명하였습니다. 이러한 결과는 삼중음성유방암에서 ELK3를 억제함으로서 암 전이를 억제하고 동시에 항암 면역 치료 효능을 향상시킬수 있음을 시사합니다.- 최승희(차의과학대학교)
댓글 작성 로그인
팝업 닫기관련 링크
연구자 키워드
관련분야 연구자보기
소속기관 논문보기
관련분야 논문보기
해당논문 저자보기
