Troponin-I enhances and is required for oncogenic overgrowth
| Autor: | Sergio Casas-Tintó, Manuel Serrano, Antonio Maraver, Alberto Ferrús |
|---|---|
| Přispěvatelé: | Herrada, Anthony, Instituto Cajal, Consejo Superior de Investigaciones Científicas [Madrid] (CSIC), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Spanish National Cancer Research Center (CNIO) |
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Male MESH: Tumor Burden Lung Neoplasms Drosophila Cancer Cell competition Cell proliferation Cell Gene Expression Animals Genetically Modified Drosophila Proteins MESH: Animals cell competition musculoskeletal system MESH: RNAi Therapeutics Tumor Burden medicine.anatomical_structure Drosophila melanogaster Oncology cardiovascular system [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry Molecular Biology/Genomics [q-bio.GN] Rap1 Female RNA Interference Drosophila MESH: Troponin I MESH: Xenograft Model Antitumor Assays MESH: Gene Expression MESH: Drosophila Proteins MESH: RNA Interference Mice Nude [SDV.CAN]Life Sciences [q-bio]/Cancer Biology MESH: Drosophila melanogaster MESH: Animals Genetically Modified 03 medical and health sciences Downregulation and upregulation [SDV.CAN] Life Sciences [q-bio]/Cancer [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry Molecular Biology/Genomics [q-bio.GN] Carcinoma medicine MESH: Mice Nude Animals Humans cancer Gene MESH: Humans Cell growth Troponin I Cancer medicine.disease Xenograft Model Antitumor Assays MESH: Male MESH: Lung Neoplasms 030104 developmental biology RNAi Therapeutics cell proliferation Cell culture A549 Cells Immunology Cancer research MESH: A549 Cells MESH: Female Priority Research Paper |
| Zdroj: | Oncotarget Oncotarget, Impact journals, 2016, 7 (33), pp.52631-52642. ⟨10.18632/oncotarget.10616⟩ Digital.CSIC. Repositorio Institucional del CSIC instname |
| ISSN: | 1949-2553 |
| Popis: | Human tumors of various tissue origins show an intriguing over-expression of genes not considered oncogenes, such as that encoding Troponin-I (TnI), a wellknown muscle protein. Out of the three TnI genes known in humans, the slow form, TNNI1, is affected the most. Drosophila has only one TnI gene, wupA. Here, we studied excess- and loss-of function of wupA in Drosophila, and assayed TNNI1 down regulation in human tumors growing in mice. Drosophila TnI excess-of-function increases proliferation and potentiates oncogenic mutations in Ras, Notch and Lgl genes. By contrast, TnI loss-of-function reduces proliferation and antagonizes the overgrowth due to these oncogenic mutations. Troponin-I defective cells undergo Flower- and Sparc-dependent cell competition. TnI can localize to the nucleus and its excess elicits transcriptional up-regulation of InR, Rap1 and Dilp8, which is consistent with the increased cell proliferation. Human tumor cell lines treated with a human Troponin-I peptide arrest in G/G. In addition, proliferation of non-smallcell lung carcinoma xenografts in mice is restrained by TNNI1 down-regulation. Thus, Troponin-I reveals a novel function in cell proliferation that may be of therapeutic interest in certain types of cancer. |
| Databáze: | OpenAIRE |
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