Expression of GRP78 and phosphorylated JNK in human CCA.
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(A) GRP78 and phosphorylated JNK in human CCA were analyzed using immunohistochemistry. (B) Summary of experimental findings. In human CCA cells, the phosphorylation of eIF2α initiates ATF4 expression, which then induces GRP78 accumulation. GRP78 plays an important role in promoting human CCA cells proliferation and invasion. Suppression of mTOR inhibits eIF2α-induced ATF4 expression, which leads to a decrease in GRP78 levels. JNK blocking decreases GRP78 levels through inhibiting the activity of mTOR. Similarly, PI3K/Akt blocking decreases GRP78 levels through inhibiting the activity of mTOR.