title: KANK1 inhibits cell growth by inducing apoptosis through regulating CXXC5 in human malignant peripheral nerve sheath tumors.
abstract: Malignant peripheral nerve sheath tumors (MPNSTs) are a type of rare sarcomas with a poor prognosis due to its highly invasive nature and limited treatment options. Currently there is no targeted-cancer therapy for this type of malignancy. Thus, it is important to identify more cancer driver genes that may serve as targets of cancer therapy. Through comparative oncogenomics, we have found that KANK1 was a candidate tumor suppressor gene (TSG) for human MPNSTs. Although KANK1 is known as a cytoskeleton regulator, its tumorigenic function in MPNSTs remains largely unknown. In this study, we report that restoration of KANK1 in human MPNST cells inhibits cell growth both in human cell culture and xenograft mice by increasing apoptosis. Consistently, knockdown of KANK1 in neurofibroma cells promoted cell growth. Using RNA-seq analysis, we identified CXXC5 and other apoptosis-related genes, and demonstrated that CXXC5 is regulated by KANK1. Knockdown of CXXC5 was found to diminish KANK1-induced apoptosis in MPNST cells. Thus, KANK1 inhibits MPNST cell growth though CXXC5 mediated apoptosis. Our results suggest that KANK1 may function as a tumor suppressor in human MPNSTs, and thus it may be useful for targeted therapy.
authors.affiliation: Department of Comparative Pathobiology, Purdue University, West Lafayette, Indiana, United States.
authors.forename: Zhibin
authors.initials: Z
authors.lastname: Cui
authors.affiliation: A316 Environment and Ecology Building, Xiamen, Fujian 361102, China.
authors.forename: Yingjia
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Department of Comparative Pathobiology, Purdue University, West Lafayette, Indiana, United States.
authors.forename: Kenny H
authors.initials: KH
authors.lastname: Chen
authors.affiliation: Department of Comparative Pathobiology, Purdue University, West Lafayette, Indiana, United States.|Purdue University Center for Cancer Research, West Lafayette, Indiana, United States.|Purdue Institute for Inflammation, Immunology and Infectious Diseases (PI4D), West Lafayette, Indiana, United States.
authors.forename: Suresh K
authors.initials: SK
authors.lastname: Mittal
authors.affiliation: Purdue University Center for Cancer Research, West Lafayette, Indiana, United States.|Department of Basic Medical Sciences, Purdue University, 625 Harrison Street, West Lafayette, Indiana, 47906, USA.
authors.forename: Jer-Yen
authors.initials: JY
authors.lastname: Yang
authors.affiliation: Department of Comparative Pathobiology, Purdue University, West Lafayette, Indiana, United States.|Purdue University Center for Cancer Research, West Lafayette, Indiana, United States.|Purdue Institute for Inflammation, Immunology and Infectious Diseases (PI4D), West Lafayette, Indiana, United States.|Integrative Neuroscience Center; Purdue University, 625 Harrison Street, West Lafayette, Indiana, 47906, USA.
authors.forename: GuangJun
authors.initials: G
authors.lastname: Zhang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; D018628:Gene Dosage; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D018317:Nerve Sheath Neoplasms / Q000235:genetics* / Q000473:pathology*; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays; D015027:Zebrafish
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C540448:CXXC5 protein, human; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; C467739:KANK1 protein, human; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins