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Active Fraction from Embryo Fish Extracts Induces Reversion of the Malignant Invasive Phenotype in Breast Cancer through Down-regulation of TCTP and Modulation of E-cadherin/?-catenin Pathway.

ABSTRACT: Some yet unidentified factors released by both oocyte and embryonic microenvironments demonstrated to be non-permissive for tumor development and display the remarkable ability to foster cell/tissue reprogramming, thus ultimately reversing the malignant phenotype. In the present study we observed how molecular factors extracted from Zebrafish embryos during specific developmental phases (20 somites) significantly antagonize proliferation of breast cancer cells, while reversing a number of prominent aspects of malignancy. Embryo extracts reduce cell proliferation, enhance apoptosis, and dramatically inhibit both invasiveness and migrating capabilities of cancer cells. Counteracting the invasive phenotype is a relevant issue in controlling tumor spreading and metastasis. Moreover, such effect is not limited to cancerous cells as embryo extracts were also effective in inhibiting migration and invasiveness displayed by normal breast cells undergoing epithelial-mesenchymal transition upon TGF-?1 stimulation. The reversion program involves the modulation of E-cadherin/?-catenin pathway, cytoskeleton remodeling with dramatic reduction in vinculin, as well as downregulation of TCTP and the concomitant increase in p53 levels. Our findings highlight that-contrary to the prevailing current "dogma", which posits that neoplastic cells are irreversibly "committed"-the malignant phenotype can ultimately be "reversed", at least partially, in response to environmental morphogenetic influences.

SUBMITTER: Proietti S

PROVIDER: S-EPMC6539734 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Active Fraction from Embryo Fish Extracts Induces Reversion of the Malignant Invasive Phenotype in Breast Cancer through Down-regulation of TCTP and Modulation of E-cadherin/β-catenin Pathway.

Proietti Sara S Cucina Alessandra A Pensotti Andrea A Biava Pier Mario PM Minini Mirko M Monti Noemi N Catizone Angela A Ricci Giulia G Leonetti Erica E Harrath Abdel Halim AH Alwasel Saleh H SH Bizzarri Mariano M

International journal of molecular sciences 20190430 9

Some yet unidentified factors released by both oocyte and embryonic microenvironments demonstrated to be non-permissive for tumor development and display the remarkable ability to foster cell/tissue reprogramming, thus ultimately reversing the malignant phenotype. In the present study we observed how molecular factors extracted from Zebrafish embryos during specific developmental phases (20 somites) significantly antagonize proliferation of breast cancer cells, while reversing a number of promin ...[more]

PMID: 31052313

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Project description:Background The translationally controlled tumor protein (TCTP) is a multifunctional protein that plays important roles in immune responses, cell proliferation, tumorigenicity and cell apoptosis. Here, we examined the clinical value of TCTP in glioma patient survival and investigated the functional roles and mechanism of TCTP in glioma development. Methods TCTP expression was determined through immunohistochemical staining, immunoblotting, and quantitative real-time PCR (qRT-PCR). TCTP or TCF-4 expression was silenced using short hairpin (sh) RNA. In vitro cell proliferation was detected using MTT, BrdU and colony formation assays, and in vivo tumor growth was performed using the xenograft model. TCTP/TCF-4/?-catenin association was detected using a co-immunoprecipitation (co-IP) assay. TCF-4 transcription activity was detected using a TOPflash/FOPflash report gene assay. Wnt/?-catenin-targeted gene expression was detected through Western blotting. Results TCTP protein levels were significantly elevated in high-grade gliomas compared with low-grade gliomas and normal brain tissues. Importantly, the expression of TCTP was significantly associated with poorer overall survival and disease-free survival, and TCTP also reduced the survival rate after treatment with radiotherapy and temozolomide (RT-TMZ) for glioma patients. The ectopic expression of TCTP enhanced glioma cell proliferation both in vitro and in vivo, whereas the knockdown of TCTP inhibited this effect. Similarly, the overexpression of TCTP increased ?-catenin binding to TCF-4, TOPflash report gene transcription activity, and the expression of Wnt/?-catenin signaling target genes including c-Myc and cyclin D1; notably, the knockdown of TCTP reduced these effects. The knockdown of TCF-4 using shRNA rescued the enhanced cell proliferation induced by the overexpression of TCTP. Conclusion TCTP is associated with reduced survival of glioma patients and induces glioma tumor growth through enhanced Wnt/?-catenin signaling.

Dataset Information

Active Fraction from Embryo Fish Extracts Induces Reversion of the Malignant Invasive Phenotype in Breast Cancer through Down-regulation of TCTP and Modulation of E-cadherin/?-catenin Pathway.

Publications

Active Fraction from Embryo Fish Extracts Induces Reversion of the Malignant Invasive Phenotype in Breast Cancer through Down-regulation of TCTP and Modulation of E-cadherin/β-catenin Pathway.

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