FIGURE 3.

Activation of growth hormone receptor (GHR) signalling promotes cell migration and invasion in vitro. (A) Most activated biological functions in 4339^WT‐GHR or 4339^CA‐GHR versus 4339^GFP (p ≤ .005) inferred from global proteomic analysis. Functions associated with cellular movement are marked with an asterix. (B) Network of molecules whose expression status (up/shades of red, or down/shades of green, p < .05) is predicted to promote activation of cell movement in 4339^WT‐GHR versus 4339^GFP or 4339^CA‐GHR versus 4339^GFP (activation z‐score +.9). (C–E) In vitro cell migration assays of patient‐derived cell lines (PDCLs) 4339^WT‐GHR or 4339^CA‐GHR versus 4339^GFP with representative micrographs (C), N13‐1520^WT‐GHR or N13‐1520^CA‐GHR versus N13‐1520^GFP (D) and N14‐1525^WT‐GH versus N14‐1524^GFP (E). Y‐axis represents the percentage of increase in sphere area over 24 h. (F) In vitro cell invasion assays of 4339^WT‐GHR or 4339^CA‐GHR versus 4339^GFP and representative micrographs. Y‐axis represents the percentage of increase in sphere area over 24 h. (G) Effect of GHR signalling inhibition on in vitro migration of GBM1^{GHR high}. Cells were exposed to 20‐μg/ml hGH‐G120K for 24 h. (H) Effect of GHR expression inhibition on in vitro migration of GBM1^{GHR high}. CRISPR‐induced GHR knockdown (KD) is compared to non‐targeted control (NTC). (I) Effect of RGD peptide integrin antagonist on in vitro migration of 4339^GFP, 4339^WT‐GHR and 4339^CA‐GHR. Cells were exposed to 1‐μg/ml RGD for 24 h. *p ≤ .05; **p ≤ .01; ***p ≤ .001; ****p ≤ .0001