α-catulin drives metastasis by activating ILK and driving an αvβ3 integrin signaling axis
Journal
Cancer Research
Journal Volume
73
Journal Issue
1
Pages
428-438
Date Issued
2013
Author(s)
Liang C.-H.
Chiu S.-Y.
Hsu I.-L.
Wu Y.-Y.
Tsai Y.-T.
Ke J.-Y.
Hsu Y.-C.
Li K.-C.
Chen Y.-L.
Hong T.-M.
Abstract
α-Catulin is an oncoprotein that helps sustain 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 short-hairpin RNA-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, antiapoptosis, 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-NF-κB signaling downstream of ILK, which in turn led to increased expression of fibronectin and integrin αvβ3. Pharmacologic or antibody-mediated blockade of NF-κB or αvβ3 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 patients with NSCLC. Taken together, our study shows that α-catulin plays a critical role in cancer metastasis by activating the ILK-mediated Akt-NF-κB-αvβ3 signaling axis. ?2012 AACR.
SDGs
Other Subjects
alpha catulin; fibronectin; immunoglobulin enhancer binding protein; immunoglobulin enhancer binding protein antibody; integrin linked kinase; oncoprotein; protein antibody; protein kinase B; short hairpin RNA; unclassified drug; vitronectin receptor; vitronectin receptor antibody; angiogenesis; animal experiment; animal model; animal tissue; apoptosis; article; cancer cell culture; cancer growth; cancer invasion; cancer survival; cell migration; controlled study; disease association; enzyme activation; lung non small cell cancer; male; metastasis; mouse; nonhuman; overall survival; priority journal; protein expression; protein protein interaction; receptor blocking; signal transduction; upregulation; alpha Catenin; Animals; Blotting, Western; Carcinoma, Non-Small-Cell Lung; Enzyme Activation; Humans; Integrin alphaVbeta3; Lung Neoplasms; Male; Mice; Mice, Inbred NOD; Mice, SCID; Neoplasm Invasiveness; Protein-Serine-Threonine Kinases; Reverse Transcriptase Polymerase Chain Reaction; Signal Transduction; Transplantation, Heterologous; Two-Hybrid System Techniques
Type
journal article