PLAU1 Facilitated Proliferation, Invasion, and Metastasis via Interaction With MMP1 in Head and Neck Squamous Carcinoma.

Kun Wu,Sheng Zhang,Hanjiang Wu,Yuan-Yuan Mao,Nan-Nan Han

doi:10.3389/fonc.2021.574260

Abstract

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignant neoplasm; it is associated with high morbidity and mortality. Thus, understanding the molecular mechanisms underlying its initiation and progression is critical for establishing the most appropriate treatment strategies. We found that urokinase-type plasminogen activator (PLAU1) was upregulated and associated with poor prognosis in HNSCC. Silencing of PLAU1 inhibited the proliferation, colony-formation, migration, and invasion abilities of HNSCC cells in vitro and reduced the expression of matrix metalloproteinase 1 (MMP1), whereas PLAU1 overexpression significantly enhanced the growth, the colony-formation, migration, and invasion abilities, and the xenograft tumor growth of HNSCC cells in vivo and increased the expression of MMP1. The Co-IP assay verified that PLAU1 interacted with MMP1. A positive correlation between PLAU1 and MMP1 expression was observed in HNSCC samples. si-RNAs against MMP1 reversed the aggressive effects of PLAU1 overexpression in HNSCC. Taken together, our data revealed that PLAU1 facilitated HNSCC cell proliferation, invasion, and metastasis via interaction with MMP1.

Highlights

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignant neoplasm; it is associated with high morbidity and mortality [1, 2], with approximately 800,000 new HNSCC cases reported annually worldwide [3]
An analysis of The Cancer Genome Atlas (TCGA) database further revealed that PLAU1 was significantly upregulated in HNSCC samples (Supplementary Figure 1A), and high levels of PLAU1 were associated with poor outcomes (Supplementary Figure 1B)
Our findings showed that PLAU1 facilitated HNSCC cell proliferation, invasion, and metastasis via interaction with matrix metalloproteinase 1 (MMP1)

Summary

Introduction

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignant neoplasm; it is associated with high morbidity and mortality [1, 2], with approximately 800,000 new HNSCC cases reported annually worldwide [3]. Malignant tumor recurrence and metastasis continues to be responsible for the adverse effects of HNSCC treatments, which has led to poor outcomes, including the occurrence of relapses [5]. A better understanding of the molecular mechanisms underlying HNSCC initiation and progression is critical for establishing the most appropriate treatment strategies for this condition. Urokinase-type plasminogen activator (PLAU1), which is overexpressed in different human cancer types [6,7,8,9], encodes a secreted serine protease that converts plasminogen to plasmin; this enzyme can promote tumor cell invasion and metastasis by degrading the components surrounding. The biological role and molecular mechanisms underlying the action of PLAU1 in HNSCC cells have not yet been elucidated

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Conclusion