{"title":"Anillin interacts with RhoA to promote tumor progression in anaplastic thyroid cancer by activating the PI3K/AKT pathway.","authors":"Shi-Tong Yu, Bai-Hui Sun, Jun-Na Ge, Zhi-Gang Wei, Zhi-Cheng Zhang, Wei-Sheng Chen, Ting-Ting Li, Shang-Tong Lei","doi":"10.1007/s12020-024-04145-z","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Anaplastic thyroid cancer (ATC) is the most aggressive thyroid malignancy and has an extremely poor prognosis, necessitating novel therapeutic strategies. This study investigated the role of anillin (ANLN) in ATC, focusing on its impact on tumor growth and metastasis through the RhoA/PI3K/AKT signaling pathway.</p><p><strong>Methods: </strong>TCGA and GEO datasets were analyzed to identify key molecular alterations in thyroid cancer. ANLN expression was assessed in clinical samples. Functional assays, including CCK-8, colony formation, scratch, and Transwell invasion assays, and mouse xenograft models, were conducted to evaluate the biological role of ANLN. Coimmunoprecipitation, immunofluorescence, and active Rho GTPase pull-down assays, as well as phosphorylation antibody arrays, were used to explore the underlying mechanisms.</p><p><strong>Results: </strong>Analysis of TCGA and GEO datasets revealed that ANLN is upregulated in thyroid cancers, including ATC and PTC, with higher ANLN expression correlating with worse survival outcomes. Functional studies demonstrated that ANLN promoted ATC cell proliferation, migration, and invasion. In vivo, ANLN knockdown inhibited tumor growth in xenograft models. Mechanistically, ANLN directly interacted with RhoA, facilitating its activation and subsequent stimulation of the PI3K/AKT signaling pathway. The tumorigenic effects of ANLN were suppressed by AKT inhibition with afuresertib or RhoA silencing.</p><p><strong>Conclusion: </strong>ANLN plays a crucial role in ATC progression by activating the RhoA/PI3K/AKT pathway, suggesting its potential as a therapeutic target in ATC.</p>","PeriodicalId":49211,"journal":{"name":"Endocrine","volume":" ","pages":""},"PeriodicalIF":3.0000,"publicationDate":"2024-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Endocrine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s12020-024-04145-z","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
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Abstract
Background: Anaplastic thyroid cancer (ATC) is the most aggressive thyroid malignancy and has an extremely poor prognosis, necessitating novel therapeutic strategies. This study investigated the role of anillin (ANLN) in ATC, focusing on its impact on tumor growth and metastasis through the RhoA/PI3K/AKT signaling pathway.
Methods: TCGA and GEO datasets were analyzed to identify key molecular alterations in thyroid cancer. ANLN expression was assessed in clinical samples. Functional assays, including CCK-8, colony formation, scratch, and Transwell invasion assays, and mouse xenograft models, were conducted to evaluate the biological role of ANLN. Coimmunoprecipitation, immunofluorescence, and active Rho GTPase pull-down assays, as well as phosphorylation antibody arrays, were used to explore the underlying mechanisms.
Results: Analysis of TCGA and GEO datasets revealed that ANLN is upregulated in thyroid cancers, including ATC and PTC, with higher ANLN expression correlating with worse survival outcomes. Functional studies demonstrated that ANLN promoted ATC cell proliferation, migration, and invasion. In vivo, ANLN knockdown inhibited tumor growth in xenograft models. Mechanistically, ANLN directly interacted with RhoA, facilitating its activation and subsequent stimulation of the PI3K/AKT signaling pathway. The tumorigenic effects of ANLN were suppressed by AKT inhibition with afuresertib or RhoA silencing.
Conclusion: ANLN plays a crucial role in ATC progression by activating the RhoA/PI3K/AKT pathway, suggesting its potential as a therapeutic target in ATC.
期刊介绍：
Well-established as a major journal in today’s rapidly advancing experimental and clinical research areas, Endocrine publishes original articles devoted to basic (including molecular, cellular and physiological studies), translational and clinical research in all the different fields of endocrinology and metabolism. Articles will be accepted based on peer-reviews, priority, and editorial decision. Invited reviews, mini-reviews and viewpoints on relevant pathophysiological and clinical topics, as well as Editorials on articles appearing in the Journal, are published. Unsolicited Editorials will be evaluated by the editorial team. Outcomes of scientific meetings, as well as guidelines and position statements, may be submitted. The Journal also considers special feature articles in the field of endocrine genetics and epigenetics, as well as articles devoted to novel methods and techniques in endocrinology.
Endocrine covers controversial, clinical endocrine issues. Meta-analyses on endocrine and metabolic topics are also accepted. Descriptions of single clinical cases and/or small patients studies are not published unless of exceptional interest. However, reports of novel imaging studies and endocrine side effects in single patients may be considered. Research letters and letters to the editor related or unrelated to recently published articles can be submitted.
Endocrine covers leading topics in endocrinology such as neuroendocrinology, pituitary and hypothalamic peptides, thyroid physiological and clinical aspects, bone and mineral metabolism and osteoporosis, obesity, lipid and energy metabolism and food intake control, insulin, Type 1 and Type 2 diabetes, hormones of male and female reproduction, adrenal diseases pediatric and geriatric endocrinology, endocrine hypertension and endocrine oncology.
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