title: Regulation of cell survival by the HIP-55 signaling network.
abstract: HIP-55 (hematopoietic progenitor kinase 1 [HPK1]-interacting protein of 55 kDa) is the mammalian homologue of the yeast Abp1p. It contains a C-terminal Src homology 3 domain and an N-terminal actin depolymerization factor (ADF-H/C) domain. HIP-55 appears to be critical for organ development and immune response and is important for the regulation of the actin cytoskeleton through its interactions with F-actin and various cytoskeletal and cell signaling proteins. However, the function of HIP-55 in tumors remains unknown. Here, we found that HIP-55 is up-regulated or down-regulated in several types of tumor tissues in patients. Of these, lung cancer tissues had the highest expression of HIP-55. To gain full insight into the function of HIP-55 in lung cancer, microarray assay was performed using Affymetrix U133 Plus 2.0 expression arrays in both HIP-55 knockdown and scramble control A549 cells. The ingenuity pathway analysis tool was utilized to construct biological networks and analyze functions that might be associated with HIP-55. Functional analysis strongly suggested that HIP-55 may be involved in cancer cell survival and cell death, which was then confirmed by further experimentation. Experimental results showed that downregulation of HIP-55 decreased the viability and increased the apoptosis of A549 cells treated with the anticancer agent etoposide. Our data suggested that HIP-55 may be a newly discovered regulatory node in the growth signaling network and a new target for therapeutic interventions in proliferative disorders.
authors.affiliation: Institute of Vascular Medicine, Peking University Third Hospital, Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Ministry of Health, Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education and Beijing Key Laboratory of Cardiovasicular Receptors Research, Beijing 100191, China. lizijian@bjmu.edu.cn.
authors.forename: Chengzhi
authors.initials: C
authors.lastname: Yang
authors.forename: Zenggang
authors.initials: Z
authors.lastname: Li
authors.forename: Zhi
authors.initials: Z
authors.lastname: Shi
authors.forename: Kangmin
authors.initials: K
authors.lastname: He
authors.forename: Aiju
authors.initials: A
authors.lastname: Tian
authors.forename: Jimin
authors.initials: J
authors.lastname: Wu
authors.forename: Youyi
authors.initials: Y
authors.lastname: Zhang
authors.forename: Zijian
authors.initials: Z
authors.lastname: Li
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005047:Etoposide / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology*; D008840:Microfilament Proteins / Q000378:metabolism*; D040081:Protein Array Analysis; D015398:Signal Transduction / Q000187:drug effects; D046888:Tissue Array Analysis; D018909:src Homology Domains
chemical_list: D000970:Antineoplastic Agents; C117063:DBNL protein, human; D008840:Microfilament Proteins; D005047:Etoposide