A YAP-centered mechanotransduction loop drives collective breast cancer cell invasion.
Nat Commun
; 15(1): 4866, 2024 Jun 07.
Article
in En
| MEDLINE
| ID: mdl-38849373
ABSTRACT
Dense and aligned Collagen I fibers are associated with collective cancer invasion led by protrusive tumor cells, leader cells. In some breast tumors, a population of cancer cells (basal-like cells) maintain several epithelial characteristics and express the myoepithelial/basal cell marker Keratin 14 (K14). Emergence of leader cells and K14 expression are regarded as interconnected events triggered by Collagen I, however the underlying mechanisms remain unknown. Using breast carcinoma organoids, we show that Collagen I drives a force-dependent loop, specifically in basal-like cancer cells. The feed-forward loop is centered around the mechanotransducer Yap and independent of K14 expression. Yap promotes a transcriptional program that enhances Collagen I alignment and tension, which further activates Yap. Active Yap is detected in invading breast cancer cells in patients and required for collective invasion in 3D Collagen I and in the mammary fat pad of mice. Our work uncovers an essential function for Yap in leader cell selection during collective cancer invasion.
Full text:
1
Database:
MEDLINE
Main subject:
Transcription Factors
/
Breast Neoplasms
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Collagen Type I
/
Mechanotransduction, Cellular
/
Adaptor Proteins, Signal Transducing
/
YAP-Signaling Proteins
/
Neoplasm Invasiveness
Limits:
Animals
/
Female
/
Humans
Language:
En
Journal:
Nat Commun
/
Nature communications
Journal subject:
BIOLOGIA
/
CIENCIA
Year:
2024
Type:
Article
Affiliation country:
Netherlands