10.6084/M9.FIGSHARE.C.6239676.V1
Peng Liu
Peng
Liu
Sheng Jing Hospital
Fuqiang Zu
Fuqiang
Zu
Sheng Jing Hospital
Hui Chen
Hui
Chen
Sheng Jing Hospital
Xiaoli Yin
Xiaoli
Yin
Sheng Jing Hospital
Xiaodong Tan
Xiaodong
Tan
0000-0003-0862-1306
Sheng Jing Hospital
Exosomal DNAJB11 promotes the development of pancreatic cancer by modulating the EGFR/MAPK pathway
Abstract Pancreatic ductal adenocarcinoma (PDAC) is a malignant tumor with invasive and metastatic characteristics and poor prognosis. Intracellular protein homeostasis is associated with invasion and metastasis of pancreatic cancer, but the specific molecular mechanism remains unclear. Our previous studies have revealed that DNAJB11, a key protein in protein homeostasis, is secreted by exosomes in the supernatant of dissociated pancreatic cancer cells with high metastasis. The results from transcriptome sequencing and co-immunoprecipitation (Co-IP)-based liquid chromatography with tandem mass spectrometry (LC–MS/MS) showed that depletion of DNAJB11 levels could increase HSPA5 expression and induce endoplasmic reticulum stress through the PRKR-like endoplasmic reticulum kinase signaling pathway in pancreatic cancer cells. Furthermore, exosomal DNAJB11 promoted cell development of PC cells in vitro and in vivo. In addition, exosomal DNAJB11 could regulate the expression of EGFR and activate the downstream MAPK signaling pathway. Clinical blood samples were collected to evaluate the potential of exosome DNAJB11 as a diagnostic biomarker and therapeutic target for the treatment of pancreatic cancer. This study could provide a new theoretical basis and potential molecular targets for the treatment of pancreatic cancer.
Biochemistry
Cell Biology
Genetics
Molecular Biology
Biotechnology
Chemical Sciences not elsewhere classified
Immunology
Biological Sciences not elsewhere classified
Cancer
figshare
2022
2022-10-10
2022-10-10
Collection
10.6084/m9.figshare.c.6239676
CC BY 4.0