Abstract
LASP1 is an actin-binding protein associated with actin assembly dynamics in cancer cells. Here, we report that LASP1 is overexpressed in pancreatic ductal adenocarcinoma (PDAC) where it promotes invasion and metastasis. We found that LASP1 overexpression in PDAC cells was mediated by HIF1α through direct binding to a hypoxia response element in the LASP1 promoter. HIF1α stimulated LASP1 expression in PDAC cells in vitro and mouse tumor xenografts in vivo. Clinically, LASP1 overexpression in PDAC patient specimens was associated significantly with lymph node metastasis and overall survival. Overall, our results defined LASP1 as a direct target gene for HIF1α upregulation that is critical for metastatic progression of PDAC.
©2014 American Association for Cancer Research.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing / genetics*
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Adaptor Proteins, Signal Transducing / metabolism
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Animals
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Carcinoma, Pancreatic Ductal / genetics*
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Carcinoma, Pancreatic Ductal / metabolism
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Carcinoma, Pancreatic Ductal / pathology
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Cell Line, Tumor
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Cell Movement / physiology
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Cytoskeletal Proteins / genetics*
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Cytoskeletal Proteins / metabolism
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Female
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Heterografts
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Homeodomain Proteins / genetics*
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Homeodomain Proteins / metabolism
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Humans
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Hypoxia-Inducible Factor 1, alpha Subunit / genetics*
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Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
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LIM Domain Proteins / genetics*
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LIM Domain Proteins / metabolism
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Mice
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Mice, Nude
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Neoplasm Metastasis
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Pancreatic Neoplasms / genetics*
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Pancreatic Neoplasms / metabolism
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Pancreatic Neoplasms / pathology
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Promoter Regions, Genetic
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Transcriptional Activation
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Transfection
Substances
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Adaptor Proteins, Signal Transducing
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Cytoskeletal Proteins
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Homeodomain Proteins
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Hypoxia-Inducible Factor 1, alpha Subunit
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LASP1 protein, human
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LIM Domain Proteins
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Lasp1 protein, mouse