Faculty, Staff and Student Publications
Publication Date
10-28-2023
Journal
Nature Communications
DOI
10.1038/s41467-023-42508-8
PMID
37898598
PMCID
PMC10613206
PubMedCentral® Posted Date
10-28-2023
PubMedCentral® Full Text Version
Post-print
Abstract
Bidirectional signal transduction between tumor epithelial cells and tumor microenvironment (TME) is important for tumor development. Here we show that Lin28b/let-7 pathway is indispensable for modulating the expression of Wnt5a in tumor epithelium, which could be secreted and then up-regulates Lin28b in cancer-associated fibroblasts (CAFs). Moreover, we demonstrate that Lin28b in CAFs promoted growth of PDAC by inducing cytokine PCSK9's production. Using an orthotopic mouse model of PDAC, we find that depletion of Lin28b in CAFs reduced tumor weight, highlighting the importance of Lin28b in PDAC stroma. Thus, our study shows that the Lin28b-Wnt5a axis plays a critical role in bidirectional crosstalk between pancreatic tumor epithelium and TME and results in a pro-tumorigenic contexture.
Keywords
Animals, Mice, Cancer-Associated Fibroblasts, Carcinoma, Pancreatic Ductal, Cell Line, Tumor, Epithelium, Fibroblasts, Pancreatic Neoplasms, Proprotein Convertase 9, Tumor Microenvironment
Published Open-Access
yes
Recommended Citation
Shu, Zhaoqi; Fan, Minghe; Tu, Bo; et al., "The Lin28b/Wnt5a Axis Drives Pancreas Cancer Through Crosstalk Between Cancer Associated Fibroblasts and Tumor Epithelium" (2023). Faculty, Staff and Student Publications. 4235.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/4235
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