PRSS contributes to cetuximab resistance in colorectal cancer

Tan, Zhaoli; Gao, Lihua; Wang, Yan; Yin, Huihui; Xi, Yongyi; Wu, Xiaojie; Shao, Yong; Qiu, Weiyi; Du, Peng; Shen, Wenlong; Fu, Ling; Jia, Ru; Zhao, Chuanhua; Zhang, Yun; Zhao, Zhihu; Sun, Zhiwei; Chen, Hongxing; Hu, Xianwen; Xu, Jianming; Wang, Youliang

The PI3K/AKT and MEK/extracellular signal-regulated kinase (MEK/ERK) signaling pathways are the downstream pathways of To quantify positive PRSS1 staining, images were taken from eight areas per tissue sample. Differences in growth were determined using Student's t test and by calculating subsequent P values. ***P < 0.001, Pearson's  2 test (cetuximab effectiveness and PRSS1 positive or PRSS1 negative). (F and G) ELISA measurement of relative PRSS1 expression in PRSS1 knockdown LoVo cells (shPRSS1-1 and shPRSS1-2) compared with that in control shRNA LoVo cells (F) and in PRSS1 knockdown HT-29 cells (shPRSS1-1 and shPRSS1-3) compared with that in shSCRM HT-29 cells (G). All values are the means ± SD from three independent experiments. Differences in growth were determined using Student's t test and by calculating subsequent P values. **P < 0.01 versus control shRNA. (H and I) Differential sensitivity of PRSS1 knockdown LoVo cells (shPRSS1-1 and shPRSS1-2) to 72-hour cetuximab treatment compared with that of shSCRM LoVo cells (H) and of PRSS1-knockdown HT-29 cells (shPRSS1-1 and shPRSS1-2) to 72-hour cetuximab treatment compared with that of control shRNA HT-29 cells (I). Values are the means ± SD of n = 3 to 5 experiments. Differences in growth were determined using Student's t test and by calculating subsequent P values. **P < 0.01 versus control shRNA, *P < 0.05 versus control shRNA. (J and K) ELISA measurement of the relative expression of exogenous PRSS1 (the PRSS1 mature peptide and PRSS1 full-length peptide) in DiFi cells compared with that in vector DiFi cells (J) and of exogenous PRSS1 (the PRSS1 mature peptide and PRSS1 full-length peptide) in LoVo cells compared with that in vector LoVo cells (K). All values are the means ± SD from three independent experiments. Differences in growth were determined using Student's t test and by calculating subsequent P values. **P < 0.01 versus empty vector. (L and M) Differential sensitivity of PRSS1-overexpressing DiFi cells (the PRSS1 mature peptide and PRSS1 full-length peptide) to 72-hour cetuximab treatment compared with that of vector DiFi cells (L) and of PRSS1-overexpressing LoVo cells (the PRSS1 mature peptide and PRSS1 full-length peptide) to 72-hour cetuximab treatment compared with that of vector LoVo cells (M). Values are the means ± SD of three to five experiments. Differences in growth were determined using Student's t test and by calculating subsequent P values. **P < 0.01 versus empty vector, *P < 0.05 versus empty vector.