p53-R273H promotes cancer cell migration via upregulation of neuraminidase-1

Tao Lv; Hong Lv; Junjie Fei; Yajun Xie; Daqing Lian; Jiang Hu; Lizhou Tang; Xiaodong Shi; Jianling Wang; Shibo Zhang; Fengtian Li; Xianjie Jiang; Yong Yi

doi:10.7150/jca.44718

p53-R273H promotes cancer cell migration via upregulation of neuraminidase-1

J Cancer. 2020 Oct 4;11(23):6874-6882. doi: 10.7150/jca.44718. eCollection 2020.

Authors

Tao Lv¹, Hong Lv², Junjie Fei³, Yajun Xie⁴, Daqing Lian¹, Jiang Hu¹, Lizhou Tang¹, Xiaodong Shi¹, Jianling Wang⁵, Shibo Zhang², Fengtian Li³, Xianjie Jiang⁶, Yong Yi³

Affiliations

¹ Center for Yunnan Plateau Biological Resources Protection Utilization, College of Biological Resource and Food Engineering, Qujing Normal University, Qujing, Yunnan, China 655011.
² Hematology Department, The First People's Hospital of Qujing, Qujing, Yunnan, China 655000.
³ Center of Growth, Metabolism and Aging, and Key Laboratory of Bio-Resource and Eco-Environment, Ministry of Education, College of Life Sciences, Sichuan University, Chengdu, China 610064.
⁴ The Ministry of Education Key Laboratory of Laboratory Medical Diagnostics, the College of Laboratory Medicine, Chongqing Medical University, Chongqing, China 400016.
⁵ College of Chemistry and Environmental Science, Qujing Normal University, Qujing, Yunnan, China 655011.
⁶ The Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Cancer Research Institute, Central South University, Changsha 410078, China.

Abstract

Accumulating evidence indicates that hotspot p53 mutants have gain-of-function in promoting cell migration and tumor metastasis. However, the molecular mechanisms are not completely understood. Here, we show that a hotspot mutation, p53-R273H, promotes non-small cell lung cancer (NSCLC) cell migration and upregulates the mRNA and protein expression of neuraminidase-1 (NEU1), a sialidase involved in cell proliferation, cell migration and tumorigenesis. Silencing of NEU1 leads to upregulation of integrin β4 which significantly inhibits NSCLC cell migration induced by p53-R273H. Mechanistically, p53-R273H promotes NEU1 transcription via activation of AKT signaling. Importantly, NEU1 expression is upregulated in human NSCLC samples harboring mutant p53 and is associated with poor clinical outcome. Overall, this study highlights an important role of NEU1 in p53-R273H-induced NSCLC cell migration and provides a potential target for NSCLC diagnosis and treatment.

Keywords: AKT; ITGB4; NEU1; cell migration; p53-R273H.