Format

Send to

Choose Destination
See comment in PubMed Commons below
Cancer Res. 2013 Jan 1;73(1):428-38. doi: 10.1158/0008-5472.CAN-12-2095. Epub 2012 Oct 9.

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

Author information

1
Institute of Basic Medical Sciences, Institute of Oral Medicine, and Graduate Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan.

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.

PMID:
23047866
DOI:
10.1158/0008-5472.CAN-12-2095
[Indexed for MEDLINE]
Free full text
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire
    Loading ...
    Support Center