title: Troponin-I enhances and is required for oncogenic overgrowth.
abstract: Human tumors of various tissue origins show an intriguing over-expression of genes not considered oncogenes, such as that encoding Troponin-I (TnI), a well-known 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 G0/G1. In addition, proliferation of non-small-cell 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.
authors.affiliation: Instituto Cajal, C.S.I.C., Madrid, Spain.
authors.forename: Sergio
authors.initials: S
authors.lastname: Casas-Tintó
authors.affiliation: Centro Nacional de Investigaciones Oncológicas (CNIO), Madrid, Spain.|Institut de Recherche en Cancérologie de Montpellier, Inserm U1194-Université de Montpellier-ICM, Montpellier, France.
authors.forename: Antonio
authors.initials: A
authors.lastname: Maraver
authors.affiliation: Centro Nacional de Investigaciones Oncológicas (CNIO), Madrid, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Serrano
authors.affiliation: Instituto Cajal, C.S.I.C., Madrid, Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: Ferrús
mesh_terms: D000072283:A549 Cells; D000818:Animals; D030801:Animals, Genetically Modified; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism; D004331:Drosophila melanogaster / Q000235:genetics; D005260:Female; D015870:Gene Expression; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008819:Mice, Nude; D034622:RNA Interference; D000067492:RNAi Therapeutics / Q000379:methods; D019210:Troponin I / Q000235:genetics* / Q000378:metabolism; D047368:Tumor Burden / Q000235:genetics; D023041:Xenograft Model Antitumor Assays / Q000379:methods
chemical_list: D029721:Drosophila Proteins; D019210:Troponin I; C000604654:wupA protein, Drosophila
keywords: Drosophila; cancer; cell competition; cell proliferation