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Fig. 1 | Journal of Experimental & Clinical Cancer Research

Fig. 1

From: The JAK2/STAT3/CCND2 Axis promotes colorectal Cancer stem cell persistence and radioresistance

Fig. 1

Identification of JAK2/STAT3 pathway activation as a potential radioresistance driver through CRC patient genomic analysis and multiple validations using CRC cells. a IPA determined that 12 signaling pathways were commonly activated in the residual CRC tissues after RT (GSE15781), in primary CRC tissues with lymph node metastasis (GSE70574), and in metastatic CRC colonizing distant organs such as the liver and lungs (GSE68468). The left Y-scale indicates enrichment z-score, the size of the round symbol indicates the ratio of contributing components, and the color indicates the p-value. b JAK/STAT signaling components that were commonly involved in all three cohorts. Two genes, ATM and JAK2, had the same tendencies between expected and experimental expression. Data are presented as the fold change compared to the control (log2) with p-values. c The mRNA expression changes in 2 potential radioresistance genes were validated in HCT116, LoVo and patient-derived primary CRC cells (P#14005083 and P#21257113) after RT (2 Gy, except for P#21257113; 4 Gy). Quantitation was conducted by real-time PCR and presented as the fold change compared to the non-RT control (log2) with p-values. d The protein expression levels of JAK2 and the p-STAT family in the above CRC cells were determined by Western blot. γH2AX was used as a positive control for radiation exposure. e The expression level of p-STAT3 in HCT116 cells transfected with the shCTRL vector or the shJAK2 vector with or without RT (2 Gy) was evaluated by Western blot. f and g The cell viability after RT under JAK2 knockdown or Stattic treatment conditions was assessed by the MTT assay in HCT116 (f) and LoVo cells (g). Cells were treated with various doses of radiation and then seeded in 96-well plates. After a 72-h incubation period, cell viability was quantified as the percentage of that of the non-RT control group. The bar graph represents the mean ± SD (n = 3). Statistical analyses were implemented using one-way ANOVA followed by Dunnett’s multiple comparison test against the control group or by Student’s t-test between two groups; *, **, and *** indicate p < 0.05, p < 0.01, and p < 0.001, respectively

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