CHC promotes tumor growth and angiogenesis through regulation of HIF-1α and VEGF signaling
Journal
Cancer Letters
Journal Volume
331
Journal Issue
1
Pages
58-67
Date Issued
2013
Author(s)
Abstract
Pancreatic adenocarcinoma is an aggressive disease with a high mortality rate. In this study, we have newly generated a monoclonal antibody (mAb), Pa65-2, which specifically binds to pancreatic cancer cells and tumor blood vessels. The target protein of Pa65-2 is identified as human clathrin heavy chain (CHC). In vitro and In vivo study showed that suppression of CHC either by shRNA or by Pa65-2 inhibited tumor growth and angiogenesis. One of the key functions of CHC was to bind with the hypoxia-inducing factor (HIF)-1α protein, increasing the stability of this protein and facilitating its nuclear translocation, thereby regulating the expression of VEGF. Taken together, our findings indicate that CHC plays a role in the processes of tumorigenesis and angiogenesis. Pa65-2 antibody or CHC shRNA can potentially be used for pancreatic cancer therapy. ? 2012 Elsevier Ireland Ltd.
SDGs
Other Subjects
clathrin heavy chain; gemcitabine; hypoxia inducible factor 1alpha; immunoglobulin G; monoclonal antibody; monoclonal antibody Pa65 2; short hairpin RNA; unclassified drug; vasculotropin; animal cell; animal experiment; animal model; animal tissue; antineoplastic activity; article; cancer growth; cancer inhibition; cancer therapy; carcinogenesis; controlled study; drug efficacy; drug protein binding; enzyme repression; human; human cell; human tissue; in vitro study; in vivo study; mouse; nonhuman; pancreas adenocarcinoma; pancreas cancer; priority journal; protein expression; protein function; protein protein interaction; protein stability; protein synthesis regulation; protein targeting; protein transport; signal transduction; Adenocarcinoma; Animals; Anoxia; Antibodies, Monoclonal; Apoptosis; Blotting, Western; Cell Cycle Proteins; Cell Proliferation; Chromatin Immunoprecipitation; Electrophoretic Mobility Shift Assay; Female; Fluorescent Antibody Technique; Gene Expression Regulation, Neoplastic; Guanine Nucleotide Exchange Factors; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Immunoenzyme Techniques; Immunoprecipitation; Mice; Mice, Inbred BALB C; Mice, Inbred NOD; Mice, SCID; Neovascularization, Pathologic; Nuclear Proteins; Pancreatic Neoplasms; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Signal Transduction; Tumor Cells, Cultured; Vascular Endothelial Growth Factor A
Type
journal article