Regulation of proliferation and cell cycle by protein regulator of cytokinesis 1 in oral squamous cell carcinoma

Fanglong Wu,Yuan Tian,Xiangli Kong,Duo Li,Weihua Guo,Yurong Liu,Xiangjian Wang,Xueke Shi,Changlei Wei,Hongmei Zhou,Xiaoyu Li,Yiqing Guo,Rui Zhang

doi:10.1038/s41419-018-0618-6

Abstract

Protein regulator of cytokinesis 1 (PRC1), a microtubule-associated protein, has emerged as a critical regulator of proliferation and apoptosis, acting predominantly in numerous tumors. However, its function in oral squamous cell carcinoma (OSCC) is still unknown. To establish the roles of PRC1 in OSCC, 95 oral clinical samples (54 OSCC, 24 oral leukoplakia [OLK], and 17 normal oral mucosa) and seven oral cell lines (6 OSCC and 1 normal oral cell lines) were analyzed using a series of molecular and genomic assays both in vivo and in vitro were conducted in this study. Herein, we provide evidence demonstrating that expression of PRC1 closely correlates with the degree of epithelial dysplasia in OLK (n = 24) (p < 0.001), and the poor differentiation, large tumor volume, lymph node metastasis, and high-clinical stage in OSCC (n = 54) (p < 0.05), illustrating that PRC1 has a promotive influence on tumor progression in OSCC. Simultaneously, we observed that PRC1 knockdown in OSCC cell lines caused G2/M phase arrest (p < 0.05), inhibited cell proliferation in vitro (p < 0.05) and tumor growth in vivo (p < 0.001). Furthermore, the effects of PRC1 on the regulation of proliferation and cell cycle transition in OSCC samples were mediated by p53. The p53/PRC1/EGFR signaling pathway was found to be implicated in the tumor progression of OSCC. Based on our data, we demonstrate that PRC1 is a key factor in regulating proliferation and the cell cycle, pointing to the potential benefits of PRC1-targeted therapies for OSCC.

Highlights

Oral cancer, including oropharyngeal cancer, is, overall, the sixth most common cancer[1]
We evaluated the expression of Protein regulator of cytokinesis 1 (PRC1) in 24 oral leukoplakia (OLK) and 54 oral squamous cell carcinoma (OSCC) specimens (Fig. 1), which represent different clinicopathologic stages (Tables 1 and 2)
The positive rate and staining score were upregulated in both OLK and OSCC when compared to normal tissue (Fig. S1a, d)

Summary

Introduction

Oral cancer, including oropharyngeal cancer, is, overall, the sixth most common cancer[1]. Surgical resection, which may or may not be associated with radio and the 5-year overall survival is still about 50%. For the early staged tumors, the cure rate is an excellent nearly. 95% with a rate of local recurrence rate of less than 5%, while the cure rate drops to 20–35% for advanced tumors with frequent recurrence and regional lymph node metastasis[5,6,7]. Targeted therapy has been endorsed with the aim of guiding personalized treatment by modulating discrete molecular functions that are specific to cancer cells and not the non-malignant tissue[8]. Official journal of the Cell Death Differentiation Association

Methods

Results

Conclusion