Transcriptional control of a collagen deposition and adhesion process that promotes lung adenocarcinoma growth and metastasis

Xiaochao Tan, Priyam Banerjee, Xin Liu, Jiang Yu, Sieun Lee, Young Ho Ahn, Chad J. Creighton, Jonathan M. Kurie

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

A fibrotic stroma accumulates in advanced cancers, and invasive cancer cells migrate along collagen fibers that facilitate dissemination from the primary tumor. However, the ways in which tumor cells govern these processes remain unclear. Here, we report that the epithelial-mesenchymal transition- activating transcription factor ZEB1 increased type I collagen (Col1) secretion and enhanced tumor cell adherence to Col1. Mechanistically, ZEB1 increased the levels of α1β1 integrin (encoded by Itga1 and Itgb1) by inhibiting PP2A activity, which reduced nuclear accumulation of HDAC4 and, thereby, derepressed Itga1 gene transcription. In parallel, ZEB1 relieved the miRNA-148a-mediated silencing of Itga1. High levels of Itga1 enhanced tumor cell adherence to Col1 and were essential for Col1- induced tumor growth and metastasis. Furthermore, ZEB1 enhanced Col1 secretion by increasing the expression of a kinesin protein that facilitated transport and secretion of Col1-containing vesicles. Our findings elucidate a transcriptional mechanism by which lung adenocarcinoma cells coordinate a collagen deposition and adhesion process that facilitates tumor progression.

Original languageEnglish
Article numbere153948
JournalJCI Insight
Volume7
Issue number1
DOIs
StatePublished - 11 Jan 2022

Fingerprint

Dive into the research topics of 'Transcriptional control of a collagen deposition and adhesion process that promotes lung adenocarcinoma growth and metastasis'. Together they form a unique fingerprint.

Cite this