S49 Hepatocyte growth factor and epidermal growth factor signalling crosstalk is involved in tunneling nanotube formation in A549 human lung adenocarcinoma cells

• DOI: 10.1136/thorax-2023-btsabstracts.55
• Publication Date: 2023-11-06T15:31:05Z
• Authors: S Banerjee; G Awanis; R Johnson; S Bidula; D Warren; A Sobolewski
• Keywords: Crosstalk

<h3></h3> Non-small cell lung cancer(NSCLC) accounts for 85% of all cancer cases and is often associated with mutations in hepatocyte growth factor(HGF) epidermal factor(EGF) expression. Tunneling nanotubes(TNTs) are thin cytoplasmic connections shown to be involved long-distance intercellular communication have an important role progression. We investigated the EGF/HGF signalling pathway crosstalk TNT formation, addition defining key characteristics TNTs A549 cells. For quantification, cells were cultured treated 100ng/mL EGF/HGF/EGF+HGF 24h analysis phase-light images was undertaken using ImageJ. Pharmacological inhibition MEK,PI3K,c-Met,EGFR,Rac1,Cdc42, Arp2/3 complex siRNA-mediated knockdown Paxillin performed assess pathways. EGF,HGF EGF+HGF induced 42%,39% 46% respectively. yielded effects consistent individual EGF HGF treatments, indicating convergence pathways at receptor level. also found Ras/MAPK/MEK, PI3K/Akt regulated EGF/HGF-induced TNTs. While singular MEK or PI3K diminished EGF-induced TNTs, this not sufficient inhibit EGF+HGF-induced simultaneous MEK+PI3K required suppression basal levels. This suggests MAPK/MEK pathways, traditionally thought independent, may participating compensatory overcome inhibition. Furthermore, inhibited marking it as scaffolding protein formation. The structure observed examined by scanning electron microscopy, wherein demonstrated non-adherence substrate presence vesicles, which confirmed later trafficking DiO lipid vesicles mitochondria between via Finally, immunofluorescent labelling showed localisation novel proteins EGFR, c-Met β1-integrin, expressing classical markers F-actin α-tubulin. findings study serve a wider implication understanding mechanisms NSCLC progression chemoresistance tumour microenvironment. Future work will explore functional consequences mitochondria/organelle transfer eventually stratify patient samples HGF/EGF dual expression determine contribution treatment resistance.