An Agrin–YAP/TAZ Rigidity Sensing Module Drives EGFR‐Addicted Lung Tumorigenesis DOI Creative Commons

Reza Bayat Mokhtari,

Divyaleka Sampath,

Paige Eversole

et al.

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: March 31, 2025

Abstract Despite epidermal growth factor receptor (EGFR) is a pivotal oncogene for several cancers, including lung adenocarcinoma (LUAD), how it senses extracellular matrix (ECM) rigidity remain elusive in the context of increasing role tissue on various hallmarks cancer development. Here shown that EGFR dictates tumorigenic agrin expression cell lines, genetically engineered EGFR‐driven mouse models, and human specimens. Agrin confers substrate stiffness‐dependent oncogenic attributes to EGFR‐reliant cells. Mechanistically, mechanoactivates through (EGF)‐dependent independent modes, thereby sensitizing its activity toward localized cell‐ECM adherence bulk by fostering interactions with integrin β1. Notably, feed‐forward loop linking agrin–EGFR response YAP–TEAD mechanosensing essential tumorigenesis. Together, combined inhibition EGFR–YAP/TEAD may offer strategy reduce tumorigenesis disrupting agrin‐EGFR mechanotransduction, uncovering therapeutic vulnerability EGFR‐addicted cancers.

Language: Английский

An Agrin–YAP/TAZ Rigidity Sensing Module Drives EGFR‐Addicted Lung Tumorigenesis DOI Creative Commons

Reza Bayat Mokhtari,

Divyaleka Sampath,

Paige Eversole

et al.

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: March 31, 2025

Abstract Despite epidermal growth factor receptor (EGFR) is a pivotal oncogene for several cancers, including lung adenocarcinoma (LUAD), how it senses extracellular matrix (ECM) rigidity remain elusive in the context of increasing role tissue on various hallmarks cancer development. Here shown that EGFR dictates tumorigenic agrin expression cell lines, genetically engineered EGFR‐driven mouse models, and human specimens. Agrin confers substrate stiffness‐dependent oncogenic attributes to EGFR‐reliant cells. Mechanistically, mechanoactivates through (EGF)‐dependent independent modes, thereby sensitizing its activity toward localized cell‐ECM adherence bulk by fostering interactions with integrin β1. Notably, feed‐forward loop linking agrin–EGFR response YAP–TEAD mechanosensing essential tumorigenesis. Together, combined inhibition EGFR–YAP/TEAD may offer strategy reduce tumorigenesis disrupting agrin‐EGFR mechanotransduction, uncovering therapeutic vulnerability EGFR‐addicted cancers.

Language: Английский

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