title: HPIP is upregulated in colorectal cancer and regulates colorectal cancer cell proliferation, apoptosis and invasion.
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 overexpressed 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.
authors: 1] Affiliated Hospital of Academy of Military Medical Sciences, Beijing, People's Republic of China [2] Department of Medical Molecular Biology, Beijing Institute of Biotechnology, Beijing, People's Republic of China [3] Department of Colorectal Surgery, the Second Artillery General Hospital, Beijing, People's Republic of China.
authors: Yingying
authors: Y
authors: Feng
authors: Department of Medical Molecular Biology, Beijing Institute of Biotechnology, Beijing, People's Republic of China.
authors: Xiaojie
authors: X
authors: Xu
authors: 1] Department of Medical Molecular Biology, Beijing Institute of Biotechnology, Beijing, People's Republic of China [2] Department of Traditional Chinese Medicine, the Second Artillery General Hospital, Beijing, People's Republic of China.
authors: Yunjing
authors: Y
authors: Zhang
authors: Department of Colorectal Surgery, the Second Artillery General Hospital, Beijing, People's Republic of China.
authors: Jianhua
authors: J
authors: Ding
authors: Department of Colorectal Surgery, the Second Artillery General Hospital, Beijing, People's Republic of China.
authors: Yonggang
authors: Y
authors: Wang
authors: Laboratory of Vaccine and Antibody Engineering, Beijing Institute of Biotechnology, Beijing, People's Republic of China.
authors: Xiaopeng
authors: X
authors: Zhang
authors: Department of Colorectal Surgery, the Second Artillery General Hospital, Beijing, People's Republic of China.
authors: Zhe
authors: Z
authors: Wu
authors: Department of Nuclear Medicine, Peking University First Hospital, Beijing 100034, China.
authors: Lei
authors: L
authors: Kang
authors: Department of Medical Molecular Biology, Beijing Institute of Biotechnology, Beijing, People's Republic of China.
authors: Yingchun
authors: Y
authors: Liang
authors: Department of Medical Molecular Biology, Beijing Institute of Biotechnology, Beijing, People's Republic of China.
authors: LiYing
authors: L
authors: Zhou
authors: Affiliated Hospital of Academy of Military Medical Sciences, Beijing, People's Republic of China.
authors: Santai
authors: S
authors: Song
authors: Department of Colorectal Surgery, the Second Artillery General Hospital, Beijing, People's Republic of China.
authors: Ke
authors: K
authors: Zhao
authors: Department of Medical Molecular Biology, Beijing Institute of Biotechnology, Beijing, People's Republic of China.
authors: Qinong
authors: Q
authors: Ye
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002453:Cell Cycle / Q000235:genetics; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D058750:Epithelial-Mesenchymal Transition; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D064593:Heterografts; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D018797:Cell Cycle Proteins; C469750:HCFC1R1 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases