c-Met and EGFR and integrin crosstalk regulates tunnelling nanotube formation in lung adenocarcinoma cells

Cicovacki, Natalia (2026) c-Met and EGFR and integrin crosstalk regulates tunnelling nanotube formation in lung adenocarcinoma cells. Masters thesis, University of East Anglia.

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Abstract

Non-small cell lung cancer (NSCLC) accounts for over 80% of lung cancer diagnoses and remains associated with poor prognosis. Hepatocyte Growth Factor (HGF) and Epidermal Growth Factor (EGF) are implicated in NSCLC due to mutations in their respective receptors, c-Met and Epidermal Growth Factor Receptor (EGFR). Crosstalk between EGFR, c-Met and integrins is a key feature of the tumour microenvironment (TME), playing a central role in tumour progression and actin cytoskeletal reorganisation. Tunnelling nanotubes (TNTs) are thin actin-based protrusions that facilitate intercellular transfer of cargo, thus contributing to tumour progression and therapeutic resistance. While previous studies identified HGF/c-Met and β1-integrin crosstalk in TNT induction, the role of EGFR, c-Met and integrin crosstalk in TNT formation, particularly via the cytoskeletal pathway, remains unexplored.

Confirmed through non-adherence experiments and immunofluorescent labelling of F-actin, α-tubulin and organelles, HGF, EGF and HGF+EGF induced TNT formation to a similar extent to each other, highlighting crosstalk in cell signalling between HGF and EGF in inducing TNT formation. This crosstalk was observed to not occur at receptor level, highlighting downstream interactions. Whilst inhibitor experiments revealed that actin polymerisation is essential for TNT formation, it was found that key regulators of actin polymerisation, FAK, Rac1, CDC42 and N-WASP did not facilitate TNT formation. Furthermore, αV-integrin, rather than α2-integrin, was identified to mediate HGF, EGF and HGF+EGF induced TNT formation in addition to co-localising with β1-integrin, c-Met and EGFR inside TNTs, aiding the theory that focal adhesion components are essential for HGF, EGF and HGF+EGF mediated TNT formation.

To conclude, this thesis demonstrates that HGF and EGF induce TNT formation through downstream signalling crosstalk and most importantly highlights αV-integrin as a potential therapeutic target for NSCLC, possibly combining with dual EGFR/c-Met inhibiting treatments.

Item Type:	Thesis (Masters)
Faculty \ School:	Faculty of Science > School of Chemistry, Pharmacy and Pharmacology
Depositing User:	Chris White
Date Deposited:	16 Mar 2026 13:51
Last Modified:	16 Mar 2026 13:51
URI:	https://ueaeprints.uea.ac.uk/id/eprint/102350
DOI:

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