HGF/c-Met/β1-integrin signalling axis induces tunneling nanotubes in A549 lung adenocarcinoma cells

Awanis, Griselda, Banerjee, Salonee, Johnson, Robert, Raveenthiraraj, Sathuwarman, Elmeligy, Aya, Warren, Derek, Gavrilovic, Jelena ORCID: https://orcid.org/0000-0002-5312-1784 and Sobolewski, Anastasia (2023) HGF/c-Met/β1-integrin signalling axis induces tunneling nanotubes in A549 lung adenocarcinoma cells. Life Science Alliance, 6 (10). ISSN 2575-1077

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Abstract

Tunneling nanotubes (TNTs) are thin cytoplasmic extensions involved in long-distance intercellular communication and can transport intracellular organelles and signalling molecules. In cancer cells, TNT formation contributes to cell survival, chemoresistance, and malignancy. However, the molecular mechanisms underlying TNT formation are not well defined, especially in different cancers. TNTs are present in non-small cell lung cancer (NSCLC) patients with adenocarcinoma. In NSCLC, hepatocyte growth factor (HGF) and its receptor, c-Met, are mutationally upregulated, causing increased cancer cell growth, survival, and invasion. This study identifies c-Met, β1-integrin, and paxillin as novel components of TNTs in A549 lung adenocarcinoma cells, with paxillin localised at the protrusion site of TNTs. The HGF-induced TNTs in our study demonstrate the ability to transport lipid vesicles and mitochondria. HGF-induced TNT formation is mediated by c-Met and β1-integrin in conjunction with paxillin, followed by downstream activation of MAPK and PI3K pathways and the Arp2/3 complex. These findings demonstrate a potential novel approach to inhibit TNT formation through targeting HGF/c-Met receptor and β1-integrin signalling interactions, which has implications for multi-drug targeting in NSCLC.

Item Type:	Article
Additional Information:	Funding information: The authors gratefully acknowledge the funding from the School of Pharmacy, University of East Anglia (2129175FA1), Nurhadibrata Jap (100048700RA1), and Biotechnology and Biological Sciences Research Council (BB/T007699/1).
Uncontrolled Keywords:	sdg 3 - good health and well-being ,/dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_being
Faculty \ School:	Faculty of Science > School of Pharmacy Faculty of Science Faculty of Science > School of Biological Sciences
UEA Research Groups:	Faculty of Science > Research Groups > Molecular and Tissue Pharmacology Faculty of Science > Research Groups > Cells and Tissues
Depositing User:	LivePure Connector
Date Deposited:	08 May 2024 08:22
Last Modified:	13 May 2024 00:11
URI:	https://ueaeprints.uea.ac.uk/id/eprint/95088
DOI:	10.26508/lsa.202301953

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