Evidence for Critical Role of Lymphocyte Cytosolic Protein 1 in Oral Cancer

Nao Koide,Yosuke Endo-Sakamoto,Toshihiro Shimizu,Hideki Tanzawa,Isao Miyamoto,Masashi Shiiba,Atsushi Kasamatsu,Shusaku Yoshimura,Yasushi Kimura,Katsuhiro Uzawa,Sho Ishida

doi:10.1038/srep43379

Abstract

Lymphocyte cytosolic protein 1 (LCP1), a member of actin-binding protein of the plastin family, has been identified in several malignant tumors of non-hematopoietic sites, such as the colon, prostate, and breast. However, little is known about the roles of LCP1 in oral squamous cell carcinomas (OSCCs). This present study sought to clarify the clinical relevance of LCP1 in OSCCs and investigate possible clinical applications for treating OSCCs by regulating LCP1 expression. We found up-regulation of LCP1in OSCCs compared with normal counterparts using real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR), immunoblotting, and immunohistochemistry (P < 0.05). We used shRNA models for LCP1 (shLCP1) and enoxacin (ENX), a fluoroquinolone antibiotic drug, as a regulator of LCP1 expression. In addition to the LCP1 knockdown experiments in which shLCP1 cells showed several depressed functions, including cellular proliferation, invasiveness, and migratory activities, ENX-treated cells also had attenuated functions. Consistent with our hypothesis from our in vitro data, LCP1-positive OSCC samples were correlated closely with the primary tumoral size and regional lymph node metastasis. These results suggested that LCP1 is a useful biomarker for determining progression of OSCCs and that ENX might be a new therapeutic agent for treating OSCCs by controlling LCP1 expression.

Highlights

The plastin family, which is comprised of actin-binding proteins, is conserved evolutionary and expressed in such as yeast, plant, and animal cells[1]
We found that Lymphocyte cytosolic protein 1 (LCP1) was overexpressed in oral squamous cell carcinomas (OSCCs) in vitro and in vivo; LCP1 knockdown cells decreased cell growth, invasiveness, and migratory activities; and LCP1 expression in clinical samples was associated positively with tumoral size and regional lymph node metastasis in OSCCs
We focused that an oral broad-spectrum fluoroquinolone, ENX, controlled LCP1 expression, leading to similar phenotypes of LCP1 knockdown cells

Summary

Introduction

The plastin family, which is comprised of actin-binding proteins, is conserved evolutionary and expressed in such as yeast, plant, and animal cells[1]. L-plastin, lymphocyte cytosolic protein 1 (LCP1), is expressed in hematopoietic cellular lineages and many types of cancers[1]. LCP1 is overexpressed and play an important role in tumor cell functions in colon cancer, LCP1 gene serve as gender- and/or stage-specific molecular predictors of tumor recurrence as well as potential therapeutic targets[5]. Similar to those cancers, LCP1 is participated in tumoral invasion and metastasis in prostate cancer cells, and its knockdown experiment is potentially a useful approach for treating tumors[1,6]. We sought to clarify the clinical relevance of LCP1 in OSCCs and valuate a new candidate for medical treatment of OSCCs by drug repositioning of an antibiotic agent, enoxacin

Methods

Results

Conclusion