Figure - PMC

Skip to main content

An official website of the United States government

Here's how you know

Here's how you know

Official websites use .gov
A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS
A lock ( ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

View full-text article in PMC

. 2022 Feb 2;14(3):779. doi: 10.3390/cancers14030779

Search in PMC
Search in PubMed
View in NLM Catalog
Add to search

© 2022 by the authors.

Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).

PMC Copyright notice

Model summarising the relationship between ALK signalling and MT dynamics in EML4-ALK V3. Schematic model showing the proposed drug resistance mechanism of EML4-ALK V3. EML4-ALK variants, the protein exists as a trimer via the dynamic interactions of the EML4 trimerization domain that drive ALK activation and signalling, but only EML4-ALK V3 associates efficiently with microtubules to enhance stability and confer resistance to vincristine. The inactivation of ALK kinase via ALK-TKIs sequesters EMl4-ALK V3 to microtubules, promoting tubulin acetylation and chemoresistance. Additionally, EML4-ALK V3 maintains an active JAK/STAT3 pathway in the presence of ALK-TKIs. Taken together, these drug-resistance mechanisms allow EML4-ALK V3 to escape cell death.