인문학
사회과학
자연과학
공학
의약학
농수해양학
예술체육학
복합학
DBpia AI
AI 에이전트
AI 아이디어
AI 리더
AI 뷰어
Citeasy
크롬 서지관리 다운로드
지원사업
학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
커뮤니티
연구자들이 자신의 연구와 전문성을 널리 알리고, 새로운 협력의 기회를 만들 수 있는 네트워킹 공간이에요.
초록·키워드
Gastric cancer remains one of the most lethal malignancies worldwide, with high relapse rates and limited survival for patients with advanced disease. Despite advances in targeted therapies and immune checkpoint inhibition, intrinsic tumor heterogeneity poses challenges for effective treatment. The HER3 receptor (ERBB3) has emerged as an important player in cancer progression, contributing to aggressive tumor behavior and poor prognosis. Recent evidence indicates that activating ferroptosis-an iron-dependent, non-apoptotic form of cell death-offers a promising strategy to inhibit cancer growth. In gastric cancer, ferroptosis plays a crucial role, and promoting this process may open new avenues for therapeutic intervention. Ferroptosis is characterized by iron-mediated lipid peroxidation of cell membranes and is critically regulated by the cystine/glutamate antiporter system (SLC7A11) and glutathione peroxidase 4 (GPX4). Our study aimed to investigate the relationship between ERBB3 and ferroptosis in gastric cancer. We found that high ERBB3 expression correlated with resistance to ferroptosis-inducing agents, including GPX4 and SLC7A11 inhibitors, across multiple cell lines. Vice versa, ERBB3 inhibition with TX1-85-1 induced lipid peroxidation in gastric cancer cells, with effects most pronounced in cell lines expressing higher SLC7A11 levels. Knockdown of ERBB3 reproduced these effects, suggesting SLC7A11 as a predictive marker. Importantly, combined inhibition of ERBB3 and GPX4 significantly enhanced lipid peroxidation and cytotoxicity, while ERBB3 activation by co-treatment with the ERBB3 ligand heregulin reduced lipid peroxidation in cells with lower baseline SLC7A11 expression. Analysis of glutathione levels and SLC7A11 expression further supported the role of ERBB3 in modulating ferroptosis sensitivity. These findings identify ERBB3 as a critical regulator of ferroptosis and a promising target for enhancing ferroptosis-mediated cell death. Its inhibition in combination with ferroptosis inducers may thus represent a particularly promising and efficacious therapeutic strategy in gastric cancer.
인공지능 문자 인식 모델을 통해 추출된 텍스트로, 일부 오타나 오류가 포함될 수 있으나 지속적으로 개선 중입니다.
오류를 발견하셨다면 해당 부분을 드래그한 후 ' 를 통해 신고해주세요.
오류를 발견하셨다면 해당 부분을 드래그한 후 ' 를 통해 신고해주세요.
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