Dottorato in Medicina Molecolare

1: Gurrapu S, Franzolin G, Fard D, Accardo M, Medico E, Sarotto I, Sapino A,
Isella C, Tamagnone L. Reverse signaling by semaphorin 4C elicits SMAD1/5- and
ID1/3-dependent invasive reprogramming in cancer cells. Sci Signal. 2019 Aug
20;12(595):eaav2041. doi: 10.1126/scisignal.aav2041. PMID: 31431542.

2: Fard D, Tamagnone L. Semaphorins in health and disease. Cytokine Growth
Factor Rev. 2020 Sep 2:S1359-6101(20)30077-0. doi:
10.1016/j.cytogfr.2020.05.006. Epub ahead of print. PMID: 32900601.

Semaphorin 4C forward and reverse signaling in breast cancer cells

by Sreeharsha Gurrapu, Damon Fard, Giulia Franzolin, Massimo Accardo, and Luca Tamagnone

Semaphorins are a family of molecular signals guiding cell migration, furthermore implicated in the regulation of cancer cells. In particular, transmembrane semaphorins are postulated to act both as ligands, and as signaling receptors (“reverse” mode); however, semaphorin reverse signaling in cancer is poorly understood. Here we report a novel function of transmembrane Semaphorin 4C (Sema4C), acting as receptor rather than ligand to elicit E-cadherin upregulation and extensive reprogramming of gene expression, which suppressed the typical features of epithelial-mesenchymal transition in invasive carcinoma cells. This phenotype was nevertheless intriguingly coupled with metastatic behavior in vivo, consistent with the evidence that Sema4C expression correlates with metastatic progression in human breast cancers. In sum, Sema4C reverse signaling promoted gene expression reprogramming and phenotypic plasticity in invasive cancer cells.

(Poster presentation at EMBO Workshop “Neural Guidance Proteins in Health and Disease”, Baveno, May 2019)

EMBO Workshop “Neural Guidance Proteins in Health and Disease”, Baveno, May 2019