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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 <jats:italic>KANK1<\/jats:italic> was a candidate tumor suppressor gene (TSG) for human MPNSTs. Although <jats:italic>KANK1<\/jats:italic> is known as a cytoskeleton regulator, its tumorigenic function in MPNSTs remains largely unknown. In this study, we report that restoration of <jats:italic>KANK1<\/jats:italic> in human MPNST cells inhibits cell growth both in human cell culture and xenograft mice by increasing apoptosis. Consistently, knockdown of <jats:italic>KANK1<\/jats:italic> in neurofibroma cells promoted cell growth. Using RNA-seq analysis, we identified <jats:italic>CXXC5<\/jats:italic> and other apoptosis-related genes, and demonstrated that <jats:italic>CXXC5<\/jats:italic> is regulated by KANK1. Knockdown of <jats:italic>CXXC5<\/jats:italic> was found to diminish KANK1-induced apoptosis in MPNST cells. Thus, KANK1 inhibits MPNST cell growth though CXXC5 mediated apoptosis. Our results suggest that <jats:italic>KANK1<\/jats:italic> may function as a tumor suppressor in human MPNSTs, and thus it may be useful for targeted therapy.<\/jats:p>","DOI":"10.1038\/srep40325","type":"journal-article","created":{"date-parts":[[2017,1,9]],"date-time":"2017-01-09T10:16:42Z","timestamp":1483957002000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["KANK1 inhibits cell growth by inducing apoptosis through regulating CXXC5 in human malignant peripheral nerve sheath tumors"],"prefix":"10.1038","volume":"7","author":[{"given":"Zhibin","family":"Cui","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingjia","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenny H.","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suresh K.","family":"Mittal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jer-Yen","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"GuangJun","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,1,9]]},"reference":[{"key":"BFsrep40325_CR1","doi-asserted-by":"publisher","first-page":"2006","DOI":"10.1002\/1097-0142(19860515)57:10<2006::AID-CNCR2820571022>3.0.CO;2-6","volume":"57","author":"BS Ducatman","year":"1986","unstructured":"Ducatman, B. 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