α-catulin drives metastasis by activating ILK and driving an αvβ3 integrin signaling axis

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Title:	α-catulin drives metastasis by activating ILK and driving an αvβ3 integrin signaling axis
Authors:	許藝瓊;Liang, Chen-Hsien;Chiu, Szu-Ying;Hsu, I-Ling;Wu, Yi-Ying;Tsai, Yao-Tsung;Ke, Jhen-Yu;Pan, Szu-Hua;Hsu, Yi-Chiung;Li, Ker-Chau;Yang, Pan-Chyr;Chen, Yuh-Ling;Hong, Tse-Ming
Contributors:	生醫理工學院生醫科學與工程學系
Keywords:	alpha Catenin - metabolism;Animals;Biological and medical sciences;Blotting, Western;Carcinoma, Non-Small-Cell Lung - metabolism;Carcinoma, Non-Small-Cell Lung - pathology;Enzyme Activation - physiology;Humans;Integrin alphaVbeta3;Lung Neoplasms - metabolism;Lung Neoplasms - pathology;Male;Medical sciences;Mice;Mice, Inbred NOD;Mice, SCID;Neoplasm Invasiveness - pathology;Protein-Serine-Threonine Kinases - metabolism;Reverse Transcriptase Polymerase Chain Reaction;Signal Transduction - physiology;Transplantation, Heterologous;Tumors;Two-Hybrid System Techniques
Date:	2013-01-01
Issue Date:	2026-04-23 11:23:29 (UTC+8)
Publisher:	American Association for Cancer Research Inc.;Philadelphia, PA: American Association for Cancer Research
Abstract:	摘要： 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. Cancer Res; 73(1); 428–38. ©2012 AACR. 其他題名： Cancer Res 出版者： Philadelphia, PA: American Association for Cancer Research 出版日期： 2013-01-01 出處： Cancer research (Chicago, Ill.), 2013-01, Vol.73 (1), p.428-438 版權： 2014 INIST-CNRS 識別號： ISSN: 0008-5472 識別號： ISSN: 1538-7445 識別號： EISSN: 1538-7445 識別號： DOI: 10.1158/0008-5472.CAN-12-2095 識別號： PMID: 23047866 識別號： CODEN: CNREA8
Appears in Collections:	[Department of Biomedical Sciences and Engineering ] journal & Dissertation

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