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

In addition, to further explore the importance of PRSS in cetuximab resistance, we assessed the influence of both knockdown and overexpression of PRSS1 on the cellular proliferation of the cell lines and found no difference in growth between the original cell lines and the PRSS1 knockdown cell lines (fig. S1H) or PRSS1 overexpression cell lines ( fig. S1I ). Then, we used the supernatants of HT-29, LoVo, and PRSS1-overexpressing DiFi cells to culture DiFi cells. We found that cells with enhanced expression of PRSS have a paracrine effect and reduce the sensitivity of neighboring cells that produce less PRSS to cetuximab, which further indicated that PRSS contributes to cetuximab resistance (fig. S1, J and K). Together, our results show that PRSS1 expression down-regulation confers cetuximab sensitivity; conversely, PRSS1 expression up-regulation correlates with a worse response to cetuximab in colon cancer and skin cell lines, indicating that PRSS1 may contribute to cetuximab resistance in mCRC.