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

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.

• Authors: Fanglong Wu, Xueke Shi, Rui Zhang, Yuan Tian, Xiangjian Wang, Changlei Wei, Duo Li, Xiaoyu Li, Xiangli Kong, Yurong Liu, Weihua Guo, Yiqing Guo, Hongmei Zhou
• Journal: Cell death & disease (Cell Death Dis) Vol. 9 Issue 5 Pg. 564 (05 01 2018) ISSN: 2041-4889 [Electronic] England
• PMID: 29752448 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cell Cycle Proteins
• Neoplasm Proteins
• PRC1 protein, human

Topics

• Carcinoma, Squamous Cell (genetics, metabolism, pathology)
• Cell Cycle Proteins (genetics, metabolism)
• Cell Line, Tumor
• G2 Phase Cell Cycle Checkpoints
• Humans
• Lymphatic Metastasis
• M Phase Cell Cycle Checkpoints
• Mouth Neoplasms (genetics, metabolism, pathology)
• Neoplasm Proteins (genetics, metabolism)
• Signal Transduction