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. 2019 Mar 12;9:137. doi: 10.3389/fonc.2019.00137

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Copyright © 2019 Sun, Chen, Zhang, Wang, Yang and Lin.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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GRP78 is the upper reaches of the Smad2/3, Src and MAPK pathways in hypoxia-induced EMT in A549 cells. (A) The mRNA relative value (control group) of EMT transcription factors is plotted (mean ± SD in three separate experiments). *P < 0.05, compared with EMT transcription factors in A549 cells under hypoxia condition separately inhibited by Smad2/3, Src, p38, ERK, and JNK inhibitors, the expression is higher than that in GRP78 knockdown A549 cells under hypoxia. (B) The protein relative value (GAPDH) of EMT markers was examined by Western blot analysis and plotted (mean ± SD in three separate experiments). *P < 0.05, compared with EMT markers of A549 cells under hypoxia condition separately inhibited by Smad2/3, Src, p38, ERK, and JNK inhibitors, the expression is higher than that in GRP78 knockdown A549 cells in the hypoxia. (A,B) indicate that the inhibition effect of GRP78 silencing is more powerful than those of the five other inhibitors. (C) The protein relative values (GAPDH) of Smad2/3, Src, p38, ERK, JNK, and their phosphorylated forms were examined by Western blot analysis and plotted (mean ± SD in three separate experiments). *P < 0.05, compared with A549 cells under hypoxia, the expression levels of Smad2/3, Src, p38, ERK, JNK, and their activation forms decrease compared with those in GRP78 knockdown A549 cells under hypoxia. After GRP78 silencing, the expression and activation of these proteins are inhibited significantly.