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

Chen Hsien Liang, Szu Ying Chiu, I. Ling Hsu, Yi Ying Wu, Yao Tsung Tsai, Jhen Yu Ke, Szu Hua Pan, Yi Chiung Hsu, Ker Chau Li, Pan Chyr Yang, Yuh Ling Chen, Tse Ming Hong

Research output: Contribution to journalArticle

22 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)428-438
Number of pages11
JournalCancer Research
Volume73
Issue number1
DOIs
Publication statusPublished - 2013 Jan 1

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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