Fig. 7
p68 overexpression augments lung metastasis. a Representative images of lungs with metastatic nodules developed after 30 days of inoculation of stable CT26EVand CT26p68 cells into the tail vein of BALB/c mice; n = 6 (top panel). Corresponding H&E-stained images of lung tissue sections containing metastatic nodules captured at 200X magnification (bottom panel). b Data represents the number and diameter of metastatic nodules in the lungs derived from CT26p68 cells relative to the CT26EV cells. c Representative images depicting IHC staining of p68, RelA (top); Bcl-2, Bcl-xL, Survivin (middle) and Snail, Vimentin and PCNA (bottom) conducted in lung metastatic nodules containing tumor tissue sections. Images were captured at 200X magnification. d Comparison of the average H-scores of the indicated proteins. Error bars in (b & d) represent mean (+) s.d. from independent biological repeats (n = 6); P < 0.0001 is represented as **** (Student’s t-test). e Model: schematic representation, depicting p68 coactivation of β-catenin in upregulation of RelA transcriptional activity and the subsequent effect on NF-κB signaling driven tumorigenesis in colon cancer. The inceptive event is triggered by p68, it cooperates with β-catenin in occupying the TBE sites in the promoter of RelA and significantly upregulates RelA transcription. This escalates RelA import to the nucleus leading to enhanced NF-κB complex activation and potentiates its transcriptional activity, manifested by the upregulation of its target genes such as Bcl-2, Bcl-xL, Survivin and XIAP. Elevated expression of these proto-oncogenes paves the way for enhanced rate of cell proliferation, survival, invasion, migration, metastasis and evasion of apoptosis, thus cumulatively contributing to oncogenesis