The interaction between S100A2 and KPNA2 mediates NFYA nuclear import and is a novel therapeutic target for colorectal cancer metastasis

Fengyan Han; Lei Zhang; Shaoxia Liao; Yanmin Zhang; Lili Qian; Feijun Hou; Jingwen Gong; Maode Lai; Honghe Zhang

doi:10.1038/s41388-021-02116-6

The interaction between S100A2 and KPNA2 mediates NFYA nuclear import and is a novel therapeutic target for colorectal cancer metastasis

Oncogene. 2022 Jan;41(5):657-670. doi: 10.1038/s41388-021-02116-6. Epub 2021 Nov 20.

Authors

Fengyan Han^#¹, Lei Zhang^#^{2

3

4}, Shaoxia Liao¹, Yanmin Zhang⁵, Lili Qian¹, Feijun Hou¹, Jingwen Gong^{2

3}, Maode Lai^{6

7

8}, Honghe Zhang^{9

10

11}

Affiliations

¹ Department of Pathology and Women's Hospital, Zhejiang University School of Medicine, Research Unit of Intelligence Classification of Tumor Pathology and Precision Therapy, Chinese Academy of Medical Sciences (2019RU042), Hangzhou, 310058, Zhejiang, China.
² Key Laboratory of Disease Proteomics of Zhejiang Province, Hangzhou, 310058, Zhejiang, China.
³ Cancer Center, Zhejiang University, Hangzhou, 310058, Zhejiang, China.
⁴ Department of Pharmacology, China Pharmaceutical University, Nanjing, 210009, China.
⁵ Laboratory of Molecular Design and Drug Discovery, School of Science, China Pharmaceutical University, 639 Longmian Avenue, Nanjing, 211198, China.
⁶ Key Laboratory of Disease Proteomics of Zhejiang Province, Hangzhou, 310058, Zhejiang, China. lmp@zju.edu.cn.
⁷ Cancer Center, Zhejiang University, Hangzhou, 310058, Zhejiang, China. lmp@zju.edu.cn.
⁸ Department of Pharmacology, China Pharmaceutical University, Nanjing, 210009, China. lmp@zju.edu.cn.
⁹ Department of Pathology and Women's Hospital, Zhejiang University School of Medicine, Research Unit of Intelligence Classification of Tumor Pathology and Precision Therapy, Chinese Academy of Medical Sciences (2019RU042), Hangzhou, 310058, Zhejiang, China. honghezhang@zju.edu.cn.
¹⁰ Key Laboratory of Disease Proteomics of Zhejiang Province, Hangzhou, 310058, Zhejiang, China. honghezhang@zju.edu.cn.
¹¹ Cancer Center, Zhejiang University, Hangzhou, 310058, Zhejiang, China. honghezhang@zju.edu.cn.

^# Contributed equally.

PMID: 34802034
DOI: 10.1038/s41388-021-02116-6

Abstract

Nucleocytoplasmic transport of proteins is disrupted and dysregulated in cancer cells. Nuclear pore complexes and cargo proteins are two main transportation regulators. However, the mechanism regulating nucleocytoplasmic transport in cancer remains elusive. Here, we identified a S100A2/KPNA2 cotransport complex that transports the tumor-associated transcription factor NFYA in colorectal cancer (CRC). Through the S100A2/KNPA2 complex, depending on its interaction with S100A2, NFYA is transported to the nucleus and inhibits the transcriptional activity of E-cadherin, which in turn promotes CRC metastasis. Targeting the S100A2/KPNA2 binding sites with the specific inhibitor delanzomib is a potential therapeutic approach for CRC.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Active Transport, Cell Nucleus
alpha Karyopherins*

Substances

alpha Karyopherins