JNK pathway inhibition selectively primes pancreatic cancer stem cells to TRAIL-induced apoptosis without affecting the physiology of normal tissue resident stem cells.

ABSTRACT:

Objective

Successful treatment of solid cancers mandates targeting cancer stem cells (CSC) without impact on the physiology of normal tissue resident stem cells. C-Jun N-terminal kinase (JNK) signaling has been shown to be of importance in cancer. We test whether JNK inhibition would sensitize pancreatic CSCs to induction of apoptosis via low-dose TNFα-related apoptosis-inducing ligand (TRAIL).

Design

Effects of JNK inhibition (JNKi) were evaluated in vitro in functional assays, through mRNA and protein expression analysis, and in in vivo mouse studies. CSCs were enriched in anoikis-resistant spheroid culture and analyzed accordingly.

Results

We confirmed that the JNK pathway is an important regulatory pathway in pancreatic cancer stem cells and further found that JNK

SUBMITTER: Recio-Boiles A 

PROVIDER: S-EPMC4891091 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature