Open Accessp53-R273H upregulates neuropilin-2 to promote cell mobility and tumor metastasis
Author(s) -
Tao Lv,
Xianqiang Wu,
Lijuan Sun,
Qingyong Hu,
Yang Wan,
Liang Wang,
Zhiqiang Zhao,
Xiao Tu,
ZhiXiong Jim Xiao
Publication year - 2017
Publication title -
cell death and disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.482
H-Index - 111
ISSN - 2041-4889
DOI - 10.1038/cddis.2017.376
Subject(s) - metastasis , cancer research , cell migration , downregulation and upregulation , gene knockdown , cell growth , biology , microbiology and biotechnology , cell , cell culture , gene , cancer , genetics
Mounting evidence indicates that hotspot p53 mutant proteins often possess gain-of-function property in promoting cell mobility and tumor metastasis. However, the molecular mechanisms are not totally understood. In this study, we demonstrate that the hotspot mutation, p53-R273H, promotes cell migration, invasion in vitro and tumor metastasis in vivo . p53-R273H significantly represses expression of DLX2, a homeobox protein involved in cell proliferation and pattern formation. We show that p53-R273H-mediated DLX2 repression leads to upregulation of Neuropilin-2 (NRP2), a multifunctional co-receptor involved in tumor initiation, growth, survival and metastasis. p53-R273H-induced cell mobility is effectively suppressed by DLX2 expression. Furthermore, knockdown of NRP2 significantly inhibits p53-R273H-induced tumor metastasis in xenograft mouse model. Together, these results reveal an important role for DLX2-NRP2 in p53-R273H-induced cell mobility and tumor metastasis.