Reverse signaling by semaphorin 4C elicits SMAD1/5- and ID1/3-dependent invasive reprogramming in cancer cells.

Sreeharsha Gurrapu, Giulia Franzolin, Damon Fard, Massimo Accardo, Enzo Medico, Ivana Sarotto, Anna Sapino, Claudio Isella, Luca Tamagnone*

*Autore corrispondente per questo lavoro

Risultato della ricerca: Contributo in rivistaArticolo in rivista

9 Citazioni (Scopus)

Abstract

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.
Lingua originaleEnglish
pagine (da-a)1-12
Numero di pagine12
RivistaScience Signaling
Volume12
DOI
Stato di pubblicazionePubblicato - 2019

Keywords

  • SEMAPHORIN 4C
  • SMAD1/5

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