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. 2023 Dec 26;130(4):555–567. doi: 10.1038/s41416-023-02530-5

Fig. 6. TGFβ signalling contributes to brain colonisation and perivascular invasion.

Fig. 6

a Protein levels of pAKT upon treatment with TGFβ in NT vs TGFβR2 KO cells with quantification of pAKT/AKT ratio; n = 3. b Representative images of brains from ECiZSGreen mice (vasculature labelled green) injected intracranially with mCherry+ NT cells, mCherry+ TGFβR2 KO cells, or mCherry+ TGFβR2 KO cells with myrAKT rescue. Scale bar = 100 µm and insert scale bar = 500 µm. Arrows point to perivascular tumour clusters (PVTCs). Quantification of c number of PVTCs, d max distance of PVTCs from invasive front, and e bulk tumour area; NT, n = 10 mice; TGFβR2 KO, n = 8 mice; and KO+myrAKT, n = 8 mice. f A model of brain colonisation and perivascular invasion in PTEN-null vs. PTEN-expressing melanoma cells in contact with brECs. PTEN loss cooperates with perivascular TGFβ to mediate pAKT-dependent colonisation, whereas PTEN and TGFβ mediate perivascular invasion through AKT-independent mechanisms. P values were determined by Mann–Whitney for (a), one-way ANOVA with Tukey’s multiple comparison test for (c) and (e), and a Kruskal–Wallis test for (d).