Fig. 1: Cancer-associated fibroblast FAK depletion enhances tumour growth.
From: Cancer associated fibroblast FAK regulates malignant cell metabolism
Low stromal FAK expression is significantly associated with reduced overall survival in a human breast (microdissected tumour stroma analysis from 53 primary breast tumours, Finak et al. dataset) and b human pancreatic cancers (54 human pancreatic cancers with activated stroma, Stratford et al. dataset). The Cox proportional hazards (Coxph) regression analysis was performed, with the rank P value shown. See full details in Methods “Gene expression data analysis and clinical inferences” section. c Tumour growth is enhanced in FSP-Cre+; FAKfl/fl mice. FSP-Cre+; FAKfl/fl and control FSP-Cre−;FAKfl/fl mice were injected orthotopically with either syngeneic breast cancer cells (E0771, n = 10 FSP-Cre+; FAKfl/fl mice and n = 18 FSP-Cre−;FAKfl/fl mice) or pancreatic ductal adenocarcinoma cells (TB32048, n = 10 FSP-Cre+; FAKfl/fl mice and 11 FSP-Cre−;FAKfl/fl mice). FSP-Cre+; FAKfl/fl and FSP-Cre−; FAKfl/fl mice were also crossed with MMTV-PyMT mice to generate MMTV+;FSP-Cre+;FAKfl/fl and MMTV+;FSP-Cre−;FAKfl/fl mice that developed spontaneous breast tumours. E0771 and TB32048 tumour growth was enhanced in FSP-Cre+;FAKfl/fl mice and the number of tumours per mouse increased significantly in MMTV+;FSP-Cre+;FAKfl/fl when compared with control mice. n = 11 MMTV+; FSP-Cre+;FAKfl/fl and 8 MMTV+;FSP-Cre−;FAKfl/fl mice. Graphs represent mean tumour volume ± s.e.m. Bar chart represents mean no. tumours per mouse ± s.e.m. d Picrosirius red staining of late-stage tumour sections from E0711, TB32048 and MMTV-PyMT tumours in FSP-Cre+; FAKfl/fl and FSP-Cre−; FAKfl/fl mice. Scatter plots represent picrosirius red image analysis (ImageJ) for individual tumours. n = 6 FSP-Cre−; FAKfl/fl and 7 FSP-Cre+; FAKfl/fl E0771 tumours; n = 14 FSP-Cre−; FAKfl/fl and 15 FSP-Cre+; FAKfl/fl TB32048 tumours; n = 8 FSP-Cre−; FAKfl/fl and 6 FSP-Cre+; FAKfl/fl MMTV tumours. Bar chart represents mean ± s.e.m. *P < 0.05, ***P < 0.001. nsd no significant difference. Statistical analysis, two-way ANOVA (c for E0771 and TB32048 growth curves); two-sided Student’s t-test (c for MMTV data, ***P < 0.0002 and d *P < 0.05). Scale bars, 1 cm (c); 100 μm (d).
