Reverse signaling by semaphorin 4C elicits SMAD1/5- and ID1/3-dependent invasive reprogramming in cancer cells
| Autor: | Ivana Sarotto, Giulia Franzolin, Anna Sapino, Enzo Medico, Massimo Accardo, Claudio Isella, Damon Fard, Luca Tamagnone, Sreeharsha Gurrapu |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Inhibitor of Differentiation Protein 1
animal structures Semaphorins Biology SEMAPHORIN 4C SMAD1/5 Biochemistry Smad1 Protein 03 medical and health sciences 0302 clinical medicine Semaphorin Neoplasms Chlorocebus aethiops medicine Animals Humans Neoplasm Invasiveness Smad3 Protein Molecular Biology Transcription factor 030304 developmental biology 0303 health sciences Cancer Cell migration Cell Biology medicine.disease Cell biology Neoplasm Proteins 030220 oncology & carcinogenesis Cancer cell COS Cells PC-3 Cells Phosphorylation Inhibitor of Differentiation Proteins Settore BIO/17 - ISTOLOGIA Signal transduction Reprogramming Signal Transduction |
| Zdroj: | Science signaling. 12(595) |
| ISSN: | 1937-9145 |
| Popis: | Semaphorins are a family of molecular signals that guide cell migration and are implicated in the regulation of cancer cells. In particular, transmembrane semaphorins are postulated to act as both ligands ("forward" mode) and signaling receptors ("reverse" mode); however, reverse semaphorin signaling in cancer is relatively less understood. Here, we identified a previously unknown function of transmembrane semaphorin 4C (Sema4C), acting in reverse mode, to elicit nonconventional TGF-β/BMP receptor activation and selective SMAD1/5 phosphorylation. Sema4C coimmunoprecipitated with TGFBRII and BMPR1, supporting its role as modifier of this pathway. Sema4C reverse signaling led to the increased abundance of ID1/3 transcriptional factors and to extensive reprogramming of gene expression, which suppressed the typical features of the epithelial-mesenchymal transition in invasive carcinoma cells. This phenotype was nevertheless coupled with burgeoning metastatic behavior in vivo, consistent with evidence that Sema4C expression correlates with metastatic progression in human breast cancers. Thus, Sema4C reverse signaling promoted SMAD1/5- and ID1/3-dependent gene expression reprogramming and phenotypic plasticity in invasive cancer cells. |
| Databáze: | OpenAIRE |
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