TGF-β signalling
A signal that stops normal cells from dividing but, once a cancer is established, switches sides: it builds scar-like stroma, walls out immune cells, and pushes cells into a migratory state.
TGF-β binds TGFBR2/TGFBR1 (ALK5) to phosphorylate SMAD2/3, which with SMAD4 regulates transcription. Early tumour suppressor (cytostatic; SMAD4 and TGFBR2 loss in pancreatic and MSI colorectal cancer) and later promoter of EMT, CAF activation, immune exclusion (T-cell exclusion in bladder and CRC), and metastasis. Bintrafusp alfa (PD-L1/TGF-β trap) failed in phase 3 (NSCLC, biliary); galunisertib was discontinued; SRK-181 (latent TGF-β1) and dalutrafusp continue. Blocking TGF-β to re-sensitise cold tumours remains an active, unproven idea.
In one picture
A town planner who first refuses all new building (tumour suppressor) and then, corrupted, builds walls and moats around the tumour that keep the police out (immune exclusion).
Diagram
top- TGF-β traps and antibodies (mostly failed: bintrafusp alfa); latent-TGF-β1-selective agents in trials
- ALK5 inhibitors (vactosertib) with IO in trials
- Integrin αvβ6/αvβ8 blockade to prevent activation (investigational)
Notes
top- Leading programmes: Massagué (MSK, TGF-β biology and metastasis); Tauriello & Batlle (IRB Barcelona, TGF-β and immune exclusion in CRC); Sheppard (UCSF, integrin activation).
Pages like this
not linked directly; found by shared links- PathwayHippo–YAP/TAZ
Shares Invasion: proteases, adhesion & the invasive front, Fibroblast activation, desmoplasia & matrix stiffness, Epithelial–mesenchymal transition & drug efflux, Tumour microenvironment (TME) and the tag mechanism.
- PathwayAntigen presentation & immune editing
Shares Hallmark: avoiding immune destruction, NK-cell recognition: missing self & stress ligands, Hot vs cold tumours, PD-1 / PD-L1 immune checkpoint & T-cell activation and the tag mechanism.
- PathwayCancer neuroscience (nerve–tumour signalling)
Shares The metastatic cascade, Tumour microenvironment (TME), Memorial Sloan Kettering Cancer Center and the tag mechanism.
- PathwayJAK–STAT signalling
Shares Fibroblast activation, desmoplasia & matrix stiffness, PD-1 / PD-L1 immune checkpoint & T-cell activation, Memorial Sloan Kettering Cancer Center and the tag mechanism.
- PathwayCellular senescence
Shares Cold Spring Harbor Laboratory, Tumour microenvironment (TME), Memorial Sloan Kettering Cancer Center and the tag mechanism.
- PathwayClonal evolution & minimal residual disease
Shares Tumour dormancy, The metastatic cascade, Memorial Sloan Kettering Cancer Center and the tag mechanism.
- PathwayCircadian control
Shares PD-1 / PD-L1 immune checkpoint & T-cell activation, Memorial Sloan Kettering Cancer Center and the tag mechanism.
- PathwayFerroptosis & regulated cell death
Shares Epithelial–mesenchymal transition & drug efflux, Memorial Sloan Kettering Cancer Center and the tag mechanism.