The actions of transforming growth factor β (TGF-β) and bone morphogenetic proteins (BMP) in various tissues are mediated by several protein-coding target genes, which explains several of the TGF-β and BMP biological effects. In cancer these pathways play pro-tumorigenic and tumor suppressing roles depending on the tumor stage and target cell in the tumor microenvironment.
Recent examples highlight the significance of non-coding RNA genes, encoding micro-RNAs (miRNAs) or long non-coding RNAs (lncRNAs), the latter being transcripts, longer than 200 nucleotides, lacking protein coding potential. Several molecules, including mRNAs, non-coding RNAs, and proteins, known to be associated with the TGF-β pathway, have been reported as constituents in the cargo of extracellular vesicles (EVs). EVs are secreted vesicles delimited by a lipid bilayer and play critical functions in intercellular communication, including regulation of the tumor microenvironment and cancer metastasis.
By focusing on childhood medulloblastoma in the case of BMPs and on breast and lung cancer, recently published and new unpublished work will be presented and discussed on the role of these pathways and their regulation by lncRNAs and by extracellular vesicles. The seminar will aim to convince the audience that a) TGF-β-induced lncRNAs can be incorporated into the central TGF-β signaling pathways, supporting dynamic regulation of signaling. b) EV cargo generated after stimulation with TGF-β includes auto-/paracrine TGF-β protein and mRNAs that encode for TGF-β signaling regulators. c) BMP signaling plays an pro-oncogenic role in childhood medulloblastoma. ​ ​