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Copyright ©2014 Baishideng Publishing Group Inc.
World J Gastroenterol. Aug 7, 2014; 20(29): 9744-9758
Published online Aug 7, 2014. doi: 10.3748/wjg.v20.i29.9744
Figure 2
Figure 2 Schematic representation of the p38α/ERK cross-talk in colorectal cancer. A: Inhibition of MEK1 triggers phospho-activation of the p38 MAPK pathway, indicating the existence of a p38α/ERK crosstalk in CRC cells; B: p38α inhibition induces increased expression of HER3, one of the receptor tyrosine kinases (RTK) of the EGF pathway, and this effect is dependent upon the activity of FoxO3A and its cofactor SIRT1. In turn, HER3 up-regulation leads to over-activation of the MEK/ERK pathway. Moreover, p38α inhibition leads to the rescue of a pro-apoptotic program driven by the extrinsic pathway through transcriptional up-regulation of TRAIL and activation of caspase-8; C: Concomitant MEK inhibition triggers Bax-dependent apoptosis by enabling signaling propagation through t-Bid and caspase 3. Bid phosphorylation at MAPK phosphorylation sites is induced by p38α inhibition and abrogated by concomitant inhibition of MEK1.