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Proposed signaling pathways involved in TCA-induced COX-2 expression in human CCA cells. Activation of S1PR2 by TCA directly activates ERK1/2/AKt via activated G proteins or indirectly activates ERK1/2/Akt via EGFR. Activated ERK1/2/Akt further activate NF-κB and COX-2 expression by inducing phosphorylation of IKKα/β and IκB, ubiquitination and degradation of p-IκB, and nuclear translocation of NF-κB.
