HAMLET Binding to Α-actinin Facilitates Tumor Cell Detachment

M. Trulsson et al.

PLOS ONE (2011)

Institution: Lund University, Sweden

Cell Line: A549 (Lung cancer cell)

Research Area: Action of HAMLET

Tags: HoloMonitor M2, Cell morphology, carcinoma, Integrins, Cell death, Small interfering RNA, Transfection, Cell staining, Cytoskeleton, Co-immunoprecipitation

Conclusions: Cell adhesion is tightly regulated by specific molecular interactions and detachment from the extracellular matrix modifies proliferation and survival. HAMLET (Human Alpha-lactalbumin Made Lethal to Tumor cells) is a protein-lipid complex with tumoricidal activity that also triggers tumor cell detachment in vitro and in vivo, suggesting that molecular interactions defining detachment are perturbed in cancer cells. To identify such interactions, cell membrane extracts were used in Far-western blots and HAMLET was shown to bind α-actinins; major F-actin cross-linking proteins, and focal adhesion constituents. The results suggest that the interaction between HAMLET and α-actinins promotes tumor cell detachment. As α-actinins also associate with signaling molecules, cytoplasmic domains of transmembrane receptors, and ion channels, additional α-actinin-dependent mechanisms are discussed. Holomonitor M2 was used to study the cell morphology including cell area, thickness, etc.

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