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. 2014 Oct 23;15(12):1315–1329. doi: 10.15252/embr.201439392

Figure 7.

Figure 7

TXNIP and E2F1 contribute to malignant progression in a regulatory loop

A–C Inverse correlation of E2F1 and TXNIP in primary melanoma of different Breslow depth obtained by Oncomine data analysis (A), real-time PCR (B) and immunohistochemistry (C).

D TXNIP inhibits E2F1 via the p16-CDK4-RB pathway. Levels of phospho-RB, CDK4, p16, E2F1 and TXNIP are indicated. The E2F1 target survivin was used as a positive control and actin for loading.

E Schematic illustration of the E2F1-miR-224/452-TXNIP axis in early- and late-stage primary melanoma. High TXNIP levels in early primary tumors restrict E2F1 activity through p16/CDK4-induced RB hypophosphorylation. During malignant progression, the miR-224/452 cluster is induced by increasing E2F1 levels, which leads to TXNIP suppression at the tumor invasion front associated with an EMT-like phenotype, enhanced migration/invasion and metastatic dissemination.

Data information: Boxes indicate the 25 and 75% quartile surrounding the median, *P ≤ 0.05 (n = 4), Mann–Whitney U-test; **P ≤ 0.01 (n = 9), two-sided Student's t-test. The lines represent the minimum and maximum transcript levels, and circles represent outliers.