Fig. 1: Hypoxia-induced MAFF regulates tumor invasion and acts as a prognostic indicator.
From: The HIF target MAFF promotes tumor invasion and metastasis through IL11 and STAT3 signaling
a 50 hypoxia-inducible genes were identified from RCC4-VHL, a clear-cell renal cell carcinoma line with reconstituted VHL, using microarray analysis12. TCGA data from cbioportal showed that these genes were altered in most of tumor cases, specifically in breast cancer. b Dataset from GEO showed that combined expression of 50 hypoxia genes were significantly correlated with overall survival in breast cancer patients (Log-rank test, p = 0.0039, GSE19783, n = 56 with low expression, n = 56 with high expression). c DAVID gene functional classification tool20,21 classified 50 hypoxia-inducible genes into functional groups, which are correlated with “Glucose Metabolism”, “Regulation of apoptosis”, and “Positive regulation of cell migration”. d RNAi screening was performed to determine genes regulating cell invasion using endoribonuclease prepared siRNA (esiRNA) libraries (MilliporeSigma). Collagen assay with tdTomato labeled MDA-MB-231 cells showed that MAFF regulates tumor cell invasion the most among 50 hypoxia-inducible genes (bar = 500μm) n = 3 biological replicates. One-Way ANOVA with multiple comparisons. p < 0.0001. e MAFF expression on breast cancer patient tissues was evaluated by staining tissue microarrays. When compared to primary tumor tissues using ImageJ, lymph node (LN) metastatic tissues showed higher intensity of MAFF expression (n = 46 for primary tissues, n = 36 for LN metastatic tissues). One-Way ANOVA with multiple comparisons. p < 0.0001. f While MAFF expression in breast cancer patients significantly correlated with hypoxia signatures (Log-rank test, p < 0.0001, R2 = 0.314), g it was also a prognostic indicator for overall survival (OS) and distant metastasis-free survival (DMFS) in all or basal-like breast cancer patients (OS: GSE42568, n = 52 with low MAFF expression, n = 52 with high MAFF expression, p = 0.0029, DMFS: KM Plotter63, n = 117 with low MAFF expression, n = 115 with high MAFF expression, p = 0.0190). Log-rank test. Graphs represent the mean per group and error bars represent the SEM.
