Submit a comment
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.
Authors
Xiaochao Tan, Priyam Banerjee, Xin Liu, Jiang Yu, Sieun Lee, Young-Ho Ahn, Chad J. Creighton, Jonathan M. Kurie
Guidelines
The Editorial Board will only consider comments that are deemed relevant and of interest to readers. The Journal will not post data that have not been subjected to peer review; or a comment that is essentially a reiteration of another comment.
- Comments appear on the Journal’s website and are linked from the original article’s web page.
- Authors are notified by email if their comments are posted.
- The Journal reserves the right to edit comments for length and clarity.
- No appeals will be considered.
- Comments are not indexed in PubMed.
Specific requirements
- Maximum length, 400 words
- Entered as plain text or HTML
- Author’s name and email address, to be posted with the comment
- Declaration of all potential conflicts of interest (even if these are not ultimately posted); see the Journal’s conflict-of-interest policy
- Comments may not include figures
