PDS5B inhibits cell proliferation, migration, and invasion via upregulation of LATS1 in lung cancer cells

Hui Xu,Tongtong Ma,Jia Ma,Jun Xia,Fan Zhang,Wenjing Zhou,Yuyun Li,Tong Cao,Chaoqun Lian,Peter Wang,Juan Li,Linhui Wu

doi:10.1038/s41420-021-00537-6

Abstract

PDS5B (precocious dissociation of sisters 5B) plays a pivotal role in carcinogenesis and progression. However, the biological functions of PDS5B in lung cancer and its underlying mechanisms are not fully elucidated. In the present study, we used MTT assays, wound-healing assays, and transwell migration and invasion approach to examine the cell viability, migration, and invasion of non-small cell lung cancer (NSCLC) cells after PDS5B modulation. Moreover, we investigated the function of PDS5B overexpression in vivo. Furthermore, we detected the expression of PDS5B in tissue samples of lung cancer patients by immunohistochemical study. We found that upregulation of PDS5B repressed cell viability, migration, and invasion in NSCLC cells, whereas downregulation of PDS5B had the opposite effects. We also observed that PDS5B overexpression retarded tumor growth in nude mice. Notably, PDS5B positively regulated LATS1 expression in NSCLC cells. Strikingly, low expression of PDS5B was associated with lymph node metastasis in lung cancer patients. Our findings suggest that PDS5B might be a therapeutic target for lung cancer.

Highlights

Lung cancer is the most common tumor and is the first leading cause of mortality in the United States [1]
Precocious dissociation of sisters 5B (PDS5B) is an important factor for proper cohesion dynamics and protection of replication fork [23]
The Shu complex, which consists of SWS1 and SWSAP1, interacts with PDS5B and SPIDR and governs DNA repair [24]

Summary

INTRODUCTION

Lung cancer is the most common tumor and is the first leading cause of mortality in the United States [1]. It has been known that Hippo pathway negatively controls the expression of YAP and TAZ, two transcriptional co-activators. This pathway consists of several kinases such as mammalian STE20-like protein kinase 1 (MST1), MST2, large tumor suppressor 1 (LATS1), and LATS2. One study revealed that PDS5B expression is correlated with histological grade in breast cancer and the treatment efficacy of chemotherapy in breast cancer patients [18]. Another study demonstrated that miR-27a represses the expression of PDS5B in prostate cancer cells, leading to the promotion of cell viability [19]. In this study, we explored the biological functions of PDS5B in lung cancer cells and determined its underlying molecular mechanism

RESULTS

Xu et al 3

DISCUSSION

Findings

MATERIALS AND METHODS