Title HPIP is upregulated in colorectal cancer and regulates colorectal cancer cell proliferation, apoptosis and invasion
Authors Feng, Yingying
Xu, Xiaojie
Zhang, Yunjing
Ding, Jianhua
Wang, Yonggang
Zhang, Xiaopeng
Wu, Zhe
Kang, Lei
Liang, Yingchun
Zhou, LiYing
Song, Santai
Zhao, Ke
Ye, Qinong
Affiliation Acad Mil Med Sci, Affiliated Hosp, Beijing, Peoples R China.
Beijing Inst Biotechnol, Dept Med Mol Biol, Beijing, Peoples R China.
Second Artillery Gen Hosp, Dept Colorectal Surg, Beijing, Peoples R China.
Second Artillery Gen Hosp, Dept Tradit Chinese Med, Beijing, Peoples R China.
Beijing Inst Biotechnol, Lab Vaccine & Antibody Engn, Beijing, Peoples R China.
Peking Univ, Hosp 1, Dept Nucl Med, Beijing 100034, Peoples R China.
Keywords HOMEOBOX INTERACTING PROTEIN-1
MESENCHYMAL TRANSITION
GROWTH
RECEPTOR
PATHWAY
ACTIVATION
EXPRESSION
THERAPY
NETWORK
ARREST
Issue Date 2015
Publisher scientific reports
Citation SCIENTIFIC REPORTS.2015,5.
Abstract Hematopoietic pre-B cell leukemia transcription factor (PBX)-interacting protein (HPIP) was shown to play a role in cancer development and progression. However, the role of HPIP in colorectal cancer (CRC) is unknown. Here, we report that HPIP is over expressed in most of CRC patients and predicts poor clinical outcome in CRC. HPIP promotes CRC cell proliferation via activation of G1/S and G2/M checkpoint transitions, concomitant with a marked increase of the positive cell cycle regulators, including cyclin D1, cyclin A, and cyclin B1. HPIP inhibits CRC cell apoptosis accompanied by the decreased levels of BAX and PIG3, the inducers of apoptosis, and the increased level of the apoptosis inhibitor BCL2. HPIP blocks caspase-3-mediated cleavage of PARP, an important apoptosis marker. HPIP promotes CRC cell migration and invasion, and regulates epithelial-mesenchymal transition (EMT), which plays a critical role in cancer cell migration and invasion. Activation of MAPK/ERK1/2 and PI3k/AKT pathways is required for HPIP modulation of CRC cell proliferation, migration and EMT. Moreover, HPIP knockdown suppresses colorectal tumor growth in nude mice. These data highlight the important role of HPIP in CRC cell proliferation and progression and suggest that HPIP may be a useful target for CRC therapy.
URI http://hdl.handle.net/20.500.11897/341375
ISSN 2045-2322
DOI 10.1038/srep09429
Indexed SCI(E)
PubMed
Appears in Collections: 第一医院

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