ANP32B Deficiency Impairs Proliferation and Suppresses Tumor Progression by Regulating AKT Phosphorylation

Overview

Journal Cell Death Dis

Specialties Cell Biology
General Medicine

Date 2016 Feb 5

PMID 26844697

Citations 15

Authors

S Yang

L Zhou

P T Reilly

S-M Shen

P He

X-N Zhu

C-X Li

L-S Wang

T W Mak

G-Q Chen

Y Yu

Affiliations

Soon will be listed here.

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.

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