PUBLICATION

KANK1 inhibits cell growth by inducing apoptosis though regulating CXXC5 in human malignant peripheral nerve sheath tumors

Authors
Cui, Z., Shen, Y., Chen, K.H., Mittal, S.K., Yang, J.Y., Zhang, G.
ID
ZDB-PUB-181020-32
Date
2017
Source
Scientific Reports   7: 40325 (Journal)
Registered Authors
Zhang, GuangJun
Keywords
none
MeSH Terms
  • Humans
  • Carrier Proteins/genetics*
  • Carrier Proteins/metabolism
  • Zebrafish
  • Cell Proliferation/genetics
  • Animals
  • Nerve Sheath Neoplasms/genetics*
  • Nerve Sheath Neoplasms/pathology*
  • Gene Dosage
  • Gene Expression Regulation, Neoplastic*
  • Apoptosis*/genetics
  • Tumor Suppressor Proteins/metabolism*
  • Gene Knockdown Techniques
  • Mice, Inbred NOD
  • Mice, SCID
  • Cell Line, Tumor
  • Xenograft Model Antitumor Assays
(all 17)
PubMed
28067315 Full text @ Sci. Rep.
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.
Errata / Notes
This article is corrected by ZDB-PUB-220906-71 .
Genes / Markers
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Expression
Phenotype
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Mutations / Transgenics
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Human Disease / Model
Human Disease Fish Conditions Evidence
malignant peripheral nerve sheath tumorTAS
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Fish
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Orthology
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Citation
Cui, Z., Shen, Y., Chen, K.H., Mittal, S.K., Yang, J.Y., Zhang, G. (2017) KANK1 inhibits cell growth by inducing apoptosis though regulating CXXC5 in human malignant peripheral nerve sheath tumors. Scientific Reports. 7:40325.