As p38 and E-cadherin also serve a key role in epithelial-to-mesenchymal transition (EMT) and cancer metastasis, we hypothesized that the combination of aspirin and erlotinib may significantly inhibit tumor metastasis.
PDAC patient samples also provided evidence of increased STAT3 activation in PDAC tumors and MAPK1 (ERK) activation in liver metastases, implicating STAT3 and ERK as key drivers in primary tumors and metastases, respectively.
The ribosomal S6 protein kinase (RSK) family is an important effector of extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK) that could influence tumour metastasis by phosphorylating proteins in both the nuclear and cytoplasmic compartments.
We found a significant correlation of Snail with EGFR((Tyr1086)) and p38 MAPK((Thr180/Tyr182)) in primary ovarian carcinoma and with EGFR((Tyr1086)) in their corresponding metastases.
In summary, caspase-3 induces ERK activation through a ceramide-dependant, protease activity-independent mechanism, which represents a novel role of caspase-3 in tumor metastasis.