1684P - Characterisation of a novel role of MST2 in cancer cell migration in the context of head and neck cancer

Date 30 September 2012
Event ESMO Congress 2012
Session Poster presentation II
Topics Head and Neck Cancers
Translational Research
Basic Principles in the Management and Treatment (of cancer)
Presenter Carlos Escriu
Authors C. Escriu, F. Watt
  • Medical Oncology, Li Ka Shing Centre, Cancer Research UK, Cambridge Research Institute Addenbrooke's Hospital, CB2 0RE - Cambridge/UK


MST2 has so far been considered a tumour suppressor, however, its expression correlates with poor prognosis in several cancer types. We aimed to understand the unknown mechanism by which these tumours appear more aggressive in the context of head and neck cancers, where MST2 is highly expressed. We tested the role of MST2 in cell migration in automated boyden chambers and scratch wound assays in several early passage oral squamous cell cancer cell lines. Interestingly, cancer cell migration was significantly reduced in knock down cells using short hairpin and short interfering RNA knock down systems. Furthermore, overexpression of wild type MST2 promoted cell migration, whereas overexpression of kinase dead MST2 had a dominant negative effect. In 3D confocal microscopy quantification of inverted matrigel invasion assays MST2 knock down also showed reduced invasion. Trying to characterise this effect further we quantified cell attachment using confocal microscopy and image analysis in different laminin substrate concentrations. MST2 knock down cells showed a reduced cell number attachement and impaired cell spreading ability. Further image analysis of migrating cells revealed, in keeping with the attachment defect, that MST2 knock down cells had larger focal adhesions with lower proportional surface of paxillin phosphorylation than control cells. MST2 knock down cells also required a longer time for actin cytoskeleton recovery after cytochalasin D treatment, suggesting a role in actin polymerisation that could explain the cell-spreading defect. Furthermore, using automated boyden chamber assays, Akt inhibition reduced cell migration over time in a directly proportional manner to cell MST2 expression levels. We are currently testing the effect of MST2 modulation in time to metastasis and survival using a tongue injection xenograft model. We describe here a novel role for MST2 in cell migration, explained by focal adhesion architecture and activity change, and by modulating actin polymerisation. Akt inhibirors can reverse this migration effect, which may lead to MST2 potentially becoming a predictor marker of response to biological therapies in head and neck cancers.


All authors have declared no conflicts of interest.