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.

Radiotherapy targeting cancer stem cells “awakens” them to induce tumour relapse and metastasis in oral cancer

“…123 It is widely considered in the majority of cancers, including oral cancer, that CAFs could play a positive role in cancer progression through their interaction with cancer cells or paracrine signalling affecting cancer cells, including CSCs. [124][125][126][127] In the study of lung cancer, it was observed that CAFs could activate IGF1R signalling in cancer cells, which further induced the expression of Nanog in cancer cells, contributing to the promotion of the stemness of CSCs, suggesting that CAFs in the CSC niche support cancer stemness. 128 In addition, many studies have also focused on the effect of radiation on CAF functions and found that radiation can promote the secretion of various cytokines by CAFs with a positive role in cancer progression.…”

ALG3 Contributes to the Malignant Biological Properties of Oral&nbsp;Squamous&nbsp;Cell&nbsp;Carcinoma Cells Through Regulating CDK-Cyclin Pathway

“…Cellular programs such as proliferation, apoptosis, differentiation, and senescence are intimately related to the cell cycle regulatory machinery [16]. Cell cycle pathway is frequently activated in human tumors, including OSCC [17]. MCM7 performs a crucial function in controlling the progress of the cell cycle and the initiation of DNA replication [18].…”

Mechanisms of the Ase1/PRC1/MAP65 family in central spindle assembly

“…The overexpression of PRC1 can lead to cytokinesis failure and chromosomal instability, further stimulating aneuploidy and tumorigenesis. High expression of PRC1 is closely associated with several phenotypes in diverse tumours: poor differentiation, large tumour size and high clinical grade in oral squamous cell carcinomas (Wu et al, ), lymph node metastasis and poor prognosis in lung adenocarcinoma patients (Zhan et al, ), the early recurrence of hepatocellular carcinoma (Chen et al, ), chemoresistance to 5‐florouracil and Taxol, and lower survival rate of hepatocellular carcinoma patients (Wang et al, ; Liu et al, ) (Table ).…”

“…PRC1 ablation leads to G2/M phase arrest in lung adenocarcinoma (Zhan et al, ) and oral squamous cell carcinomas (Wu et al, ), but the mechanism remains unclear. PRC1 also blocks mitotic exit of hepatocellular carcinoma cells at telophase in a spindle assembly checkpoint‐independent manner involving a tumor‐suppressor p53‐dependent pathway (Liu et al, ).…”

“…PRC1 also blocks mitotic exit of hepatocellular carcinoma cells at telophase in a spindle assembly checkpoint‐independent manner involving a tumor‐suppressor p53‐dependent pathway (Liu et al, ). p53 is a G1/S and G2/M checkpoint protein, which inhibits PRC1 expression, and the p53/PRC1/EGFR signalling pathway controls cell proliferation and the cell cycle (Li, Lin, & Liu, ; Wu et al, ). p53 also regulates the Myb‐related protein B (MYBL2)‐MuvB‐Forkhead box protein M1 (FOXM1) complex to suppress the expression of PRC1 , CEP55 and mitotic kinesins in breast cancers (Wolter et al, ).…”