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Therapeutic targeting of TNIK in papillary thyroid carcinoma: a novel approach for tumor growth suppression

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机构： [1]Beijing Key Laboratory for Pediatric Diseases of Otolaryngology, Head and Neck Surgery, MOE Key Laboratory of Major Diseases in Children, Beijing Pediatric Research Institute, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health (NCCH), Beijing, China [2]Biobank for Clinical Data and Samples in Pediatrics, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health (NCCH), Beijing 100045, China [3]Department of Pathology, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health (NCCH), Beijing, China [4]Department of Otolaryngology, Head and Neck Surgery, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health (NCCH), Beijing 100045, People’s Republic of China [5]Department of Thyroid and Neck Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin, China [6]Department of Otolaryngology Head and Neck Surgery, The Fourth Affiliated Hospital of Hebei Medical University, Shijiazhuang, Hebei, China

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关键词： Papillary thyroid carcinoma TNIK Cytoskeleton Migration Therapeutic target

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Papillary thyroid carcinoma (PTC) is a common endocrine malignancy. The pathology of PTC is far from clear. As a kinase that can be targeted, the role of TNIK in PTC has not been investigated. This study was focused on the effects and molecular mechanisms of TNIK in PTC. Both public datasets and clinical specimens were used to verify TNIK expression. The effects of TNIK were investigated in both cell lines and mice models. Transcriptome analysis was used to explore the underlying mechanism of TNIK. Immunofluorescence, wound healing, and qRT-PCR assays were used to validate the mechanism of TNIK in PTC. The therapeutic effects of TNIK inhibitor NCB-0846 were evaluated by flow cytometry, western blot, and subcutaneous xenografts mice. TNIK expression was upregulated in PTC tissues. TNIK knockdown could suppress cell proliferation and tumor growth in no matter cell models or nude mice. The transcriptome analysis, GO enrichment analysis, and GSEA analysis results indicated TNIK was highly correlated with cytoskeleton, cell motility, and Wnt pathways. The mechanistic studies demonstrated that TNIK regulated cytoskeleton remodeling and promoted cell migration. NCB-0846 significantly inhibited TNIK kinase activity, induced cell apoptosis, and activated apoptosis-related proteins in a dose-dependent manner. In addition, NCB-0846 inhibited tumor growth in tumor-bearing mice. In summary, we proposed a novel regulatory mechanism in which TNIK-mediated cytoskeleton remodeling and cell migration to regulate tumor progression in PTC. TNIK is a therapeutic target in PTC and NCB-0846 would act as a novel targeted drug for PTC therapy.© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

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出版当年[2025]版：

大类 | 4 区医学

小类 | 4 区肿瘤学

最新[2025]版：

大类 | 4 区医学

小类 | 4 区肿瘤学

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Q2 ONCOLOGY

最新[2024]版：

Q2 ONCOLOGY

影响因子： 3.5 最新[2024版] 3.3 最新五年平均 3.5 出版当年[2024版] 3.3 出版当年五年平均 2.8 出版前一年[2023版]

第一作者：

第一作者机构： [1]Beijing Key Laboratory for Pediatric Diseases of Otolaryngology, Head and Neck Surgery, MOE Key Laboratory of Major Diseases in Children, Beijing Pediatric Research Institute, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health (NCCH), Beijing, China

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通讯作者：

通讯机构： [1]Beijing Key Laboratory for Pediatric Diseases of Otolaryngology, Head and Neck Surgery, MOE Key Laboratory of Major Diseases in Children, Beijing Pediatric Research Institute, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health (NCCH), Beijing, China [2]Biobank for Clinical Data and Samples in Pediatrics, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health (NCCH), Beijing 100045, China [4]Department of Otolaryngology, Head and Neck Surgery, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health (NCCH), Beijing 100045, People’s Republic of China

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Therapeutic targeting of TNIK in papillary thyroid carcinoma: a novel approach for tumor growth suppression

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