title: α-Catulin drives metastasis by activating ILK and driving an αvβ3 integrin signaling axis.
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.
authors.affiliation: Institute of Basic Medical Sciences, Institute of Oral Medicine, and Graduate Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Chen-Hsien
authors.initials: CH
authors.lastname: Liang
authors.forename: Szu-Ying
authors.initials: SY
authors.lastname: Chiu
authors.forename: I-Ling
authors.initials: IL
authors.lastname: Hsu
authors.forename: Yi-Ying
authors.initials: YY
authors.lastname: Wu
authors.forename: Yao-Tsung
authors.initials: YT
authors.lastname: Tsai
authors.forename: Jhen-Yu
authors.initials: JY
authors.lastname: Ke
authors.forename: Szu-Hua
authors.initials: SH
authors.lastname: Pan
authors.forename: Yi-Chiung
authors.initials: YC
authors.lastname: Hsu
authors.forename: Ker-Chau
authors.initials: KC
authors.lastname: Li
authors.forename: Pan-Chyr
authors.initials: PC
authors.lastname: Yang
authors.forename: Yuh-Ling
authors.initials: YL
authors.lastname: Chen
authors.forename: Tse-Ming
authors.initials: TM
authors.lastname: Hong
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000473:pathology; D004789:Enzyme Activation / Q000502:physiology; D006801:Humans; D039302:Integrin alphaVbeta3; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009361:Neoplasm Invasiveness / Q000473:pathology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*; D014183:Transplantation, Heterologous; D020798:Two-Hybrid System Techniques; D051178:alpha Catenin / Q000378:metabolism; D000099200:Scaffold Protein ILK
chemical_list: D039302:Integrin alphaVbeta3; D017346:Protein Serine-Threonine Kinases; D051178:alpha Catenin; D000099200:Scaffold Protein ILK