YWHAZ interacts with DAAM1 to promote cell migration in breast cancer

Jie Mei,Leiyu Hao,Yichao Zhu,Tao Ma,Yan Liu,Yan Zhang,Qiang Zhan,Xinqian Yu

doi:10.1038/s41420-021-00609-7

Abstract

Dishevelled-associated activator of morphogenesis 1 (DAAM1) is a critical driver in facilitating metastasis in breast cancer (BrCa). However, molecular mechanisms for the regulation of DAAM1 activation are only partially elucidated. In this research, the expression levels of YWHAZ and DAAM1 were examined by immunohistochemistry (IHC) staining in BrCa tissues. The functional roles of tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta (YWHAZ)–DAAM1 axis and their regulator microRNA-613 (miR-613) in BrCa cells and associated molecular mechanisms were demonstrated in vitro. As results, the expression levels of DAAM1 and YWHAZ were significantly upregulated in BrCa tissues compared with normal tissues and remarkably associated with poor prognosis. Besides, DAAM1 and YWHAZ were positively correlated with each other in BrCa tissues. YWHAZ interacted and colocalized with DAAM1 in BrCa cells, which was essential for DAAM1-mediated microfilament remodeling and RhoA activation. Moreover, miR-613 directly targeted both YWHAZ and DAAM1, contributing to inhibiting BrCa cells migration via blocking the complex of YWHAZ–DAAM1. To sum up, these data reveal that YWHAZ regulates DAAM1 activation, and the YWHAZ–DAAM1 complex is directly targeted by the shared post-transcriptional regulator miR-613.

Highlights

Breast cancer (BrCa) is the most commonly diagnosed malignant neoplasm in females, which has surpassed lung cancer with an estimated 2.3 million new cases in the past year [1]
Compared with para-tumor tissues, the expression levels of Dishevelled-associated activator of morphogenesis 1 (DAAM1) and YWHAZ were both upregulated in BrCa tissues (Fig. 1B), which was in accord with previous research [18, 19]
DAAM1 is a formin-like protein participating in the modulation of actin cytoskeletal rearrangement

Summary

Introduction

Breast cancer (BrCa) is the most commonly diagnosed malignant neoplasm in females, which has surpassed lung cancer with an estimated 2.3 million new cases in the past year [1]. It has been proved that both environmental and genetic threats contribute to the tumorigenesis of BrCa [2]. BrCa is a heterogeneous disease that contains a wide range of malignancies varying in molecular etiology, cellular biology, imaging appearance, and clinical manifestation [4, 5]. Benefit from earlier screening and enhancement of therapeutic strategies, the prognosis of BrCa patients is significantly improved [6]. Patients with advanced BrCa accompanied with metastasis still face a risk of death [7]. Control and management of metastasis is the key to improve the prognosis of BrCa patients

Methods

Results

Conclusion