{"title":"Enhanced mitochondrial biogenesis facilitates the development of cutaneous squamous cell carcinoma.","authors":"Ziyang Wang, Ke He, Meng Liu, Weiqiang Lv, Baochen Cheng, Guanfei Zhang, Xueqiang Wang, Mengqi Zeng, Lianying Jiao, Shujun Han, Yan Zheng, Zhihui Feng","doi":"10.1016/j.canlet.2025.217623","DOIUrl":null,"url":null,"abstract":"<p><p>Mitochondrial malfunction is traditionally viewed as a major factor in tumor growth and malignancy, while recent studies have introduced conflicting views suggesting the necessity of functional mitochondria for tumor growth. Despite these differing perspectives, the specific role of mitochondria in cutaneous squamous cell carcinoma (cSCC) remains poorly understood. In this study, we observed increased mitochondrial abundance and function during the development of cSCC. We also identified retinoic acid receptor response 1 (RARRES1), which is dramatically decreased in human cSCC samples, as a key regulator of mitochondrial homeostasis. Mechanistically, RARRES1 can translocate into mitochondria and facilitate the degradation of TFAM by binding to LONP1, thereby regulating mitochondrial biogenesis. While RARRES1 suppression unleashed TFAM to promote mitochondrial biogenesis, leading to the progression of cSCC. Targeting RARRES1-LONP1/TFAM axis shows significant potential for inhibiting cSCC development. This study reveals a unique network for regulating mitochondrial homeostasis and emphasizes the crucial role of mitochondria in cSCC development, positioning the RARRES1-LONP1/TFAM axis as promising therapeutic target for future clinical applications.</p>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":" ","pages":"217623"},"PeriodicalIF":9.1000,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cancer letters","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.canlet.2025.217623","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Mitochondrial malfunction is traditionally viewed as a major factor in tumor growth and malignancy, while recent studies have introduced conflicting views suggesting the necessity of functional mitochondria for tumor growth. Despite these differing perspectives, the specific role of mitochondria in cutaneous squamous cell carcinoma (cSCC) remains poorly understood. In this study, we observed increased mitochondrial abundance and function during the development of cSCC. We also identified retinoic acid receptor response 1 (RARRES1), which is dramatically decreased in human cSCC samples, as a key regulator of mitochondrial homeostasis. Mechanistically, RARRES1 can translocate into mitochondria and facilitate the degradation of TFAM by binding to LONP1, thereby regulating mitochondrial biogenesis. While RARRES1 suppression unleashed TFAM to promote mitochondrial biogenesis, leading to the progression of cSCC. Targeting RARRES1-LONP1/TFAM axis shows significant potential for inhibiting cSCC development. This study reveals a unique network for regulating mitochondrial homeostasis and emphasizes the crucial role of mitochondria in cSCC development, positioning the RARRES1-LONP1/TFAM axis as promising therapeutic target for future clinical applications.
期刊介绍:
Cancer Letters is a reputable international journal that serves as a platform for significant and original contributions in cancer research. The journal welcomes both full-length articles and Mini Reviews in the wide-ranging field of basic and translational oncology. Furthermore, it frequently presents Special Issues that shed light on current and topical areas in cancer research.
Cancer Letters is highly interested in various fundamental aspects that can cater to a diverse readership. These areas include the molecular genetics and cell biology of cancer, radiation biology, molecular pathology, hormones and cancer, viral oncology, metastasis, and chemoprevention. The journal actively focuses on experimental therapeutics, particularly the advancement of targeted therapies for personalized cancer medicine, such as metronomic chemotherapy.
By publishing groundbreaking research and promoting advancements in cancer treatments, Cancer Letters aims to actively contribute to the fight against cancer and the improvement of patient outcomes.