α-catulin drives metastasis by activating ILK and driving an avß3 integrin signaling axis
Menée in vitro, cette étude met en évidence un mécanisme par lequel une protéine, l'alpha-catuline, favorise le processus métastatique dans le cancer du poumon non à petites cellules
α-catulin is oncoprotein that help sustains proliferation by preventing cellular senescence. Here we report that α-catulin also drives malignant invasion and metastasis. α-catulin was upregulated in highly invasive non-small cell lung cancer (NSCLC) cell lines, where its ectopic expression or shRNA-mediated attenuation enhanced or limited invasion or metastasis, respectively. α-catulin interacted with integrin-linked kinase (ILK), a serine/threonine protein kinase implicated in cancer cell proliferation, anti-apoptosis, invasion and angiogenesis. Attenuation of ILK or α-catulin reciprocally blocked cell migration and invasion induced by the other protein. Mechanistic investigations revealed that α-catulin activated Akt-NFkB signaling downstream of ILK, which in turn led to increased expression of fibronectin and integrin avß3. Pharmacological or antibody-mediated blockade of NFkB or avß3 was sufficient to inhibit α-catulin-induced cell migration and invasion. Clinically, high levels of expression of α-catulin and ILK were associated with poor overall survival in NSCLC patients. Taken together, our study demonstrates that α-catulin plays a critical role in cancer metastasis by activating the ILK-mediated Akt-NFkB-avß3 signaling axis.