Abstract
The acidic leucine-rich nuclear phosphoprotein 32B (ANP32B) is reported to impact normal development, with Anp32b-knockout mice exhibiting smaller size and premature aging. However, its cellular and molecular mechanisms, especially its potential roles in tumorigenesis, remain largely unclear. Here, we utilize 'knockout' models, RNAi silencing and clinical cohorts to more closely investigate the role of this enigmatic factor in cell proliferation and cancer phenotypes. We report that, compared with Anp32b wild-type (Anp32b+/+) littermates, a broad panel of tissues in Anp32b-deficient (Anp32b−/−) mice are demonstrated hypoplasia. Anp32b−/− mouse embryo fibroblast cell has a slower proliferation, even after oncogenic immortalization. ANP32B knockdown also significantly inhibits in vitro and in vivo growth of cancer cells by inducing G1 arrest. In line with this, ANP32B protein has higher expression in malignant tissues than adjacent normal tissues from a cohort of breast cancer patients, and its expression level positively correlates with their histopathological grades. Moreover, ANP32B deficiency downregulates AKT phosphorylation, which involves its regulating effect on cell growth. Collectively, our findings suggest that ANP32B is an oncogene and a potential therapeutic target for breast cancer treatment.
Highlights
(ANP32) protein family are characterized by a N-terminal leucine-rich repeat domain and a C-terminal low-complexity acidic region.[1]
Cell numbers in organs such as spleen and thymus were dramatically decreased in Anp32b− / − mice (Supplementary Figure S1C), supporting that Anp32b deficiency causes a hypoplastic phenotype in multiple organs
We used three models to examine the role of acidic leucine-rich nuclear phosphoprotein 32B (ANP32B) in cell proliferation and oncogenesis
Summary
(ANP32) protein family are characterized by a N-terminal leucine-rich repeat domain and a C-terminal low-complexity acidic region.[1]. ANP32A was shown to inhibit cell transformation[15,16,17] and has reduced expression in prostate and breast cancer.[18,19] ANP32E was reported to have enhanced expression in gastric cancer,[20] and a high expression of ANP32E was associated with better survival rate in follicular lymphoma.[21] Previously we reported that ANP32B, designated as PHAPI2 or SSP29, is a negative prognostic indicator for human breast cancer.[22] Full analysis of the expression and functional role of ANP32B in cancer progression has still not been undertaken. Received 02.10.15; revised 31.12.16; accepted 04.1.16; Edited by J Chipuk proteins, is lower coincident with reduced ANP32B upon silencing and in both mouse and human cancers
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
