RRC ID 67664
Author Fujii S, Matsumoto S, Nojima S, Morii E, Kikuchi A.
Title Arl4c expression in colorectal and lung cancers promotes tumorigenesis and may represent a novel therapeutic target.
Journal Oncogene
Abstract We recently demonstrated that expression of ADP-ribosylation factor (ARF)-like 4c (Arl4c) induced by a combination of Wnt/β-catenin and epidermal growth factor/Ras signaling in normal epithelial cells grown in three-dimensional culture promotes cellular migration and proliferation, resulting in formation of tube-like structures, suggesting the involvement of Arl4c in epithelial morphogenesis. It is conceivable that there could be a common mechanism between epithelial morphogenesis and carcinogenesis. Therefore the current study was conducted to investigate whether Arl4c might be involved in tumorigenesis. Immunohistochemical analyses of tissue specimens obtained from colorectal and lung cancer patients revealed that Arl4c was not observed in non-tumor regions but was strongly expressed at high frequencies in tumor lesions. Inhibition of Wnt/β-catenin or Ras/mitogen-activated protein kinase signaling reduced Arl4c mRNA levels in HCT116 colorectal cancer cells and A549 lung cancer cells. Knockdown of Arl4c inhibited Rac activity and also prevented nuclear localization of yes-associated protein (YAP)/transcriptional co-activator with PDZ-binding motif (TAZ) in these cancer cells. Arl4c-depleted cancer cells consistently showed decreased migration, invasion and proliferation capabilities both in vitro and in vivo. Furthermore, direct injection of Arl4c small interfering RNA (siRNA) into HCT116 cell-derived tumors (in vivo treatment with siRNA) inhibited tumor growth in immunodeficient mice. These results suggest that Arl4c is involved in tumorigenesis and might represent a novel therapeutic target for suppressing proliferation and invasion of colorectal and lung cancer cells.
Volume 34(37)
Pages 4834-44
Published 2015-9-10
DOI 10.1038/onc.2014.402
PII onc2014402
PMID 25486429
MeSH ADP-Ribosylation Factors / antagonists & inhibitors* ADP-Ribosylation Factors / genetics* Adenocarcinoma / drug therapy Adenocarcinoma / genetics* Adenocarcinoma / pathology Adult Aged Aged, 80 and over Animals Cell Transformation, Neoplastic / genetics* Cell Transformation, Neoplastic / pathology Colorectal Neoplasms / drug therapy Colorectal Neoplasms / genetics* Colorectal Neoplasms / pathology Gene Expression Regulation, Neoplastic / drug effects HCT116 Cells HEK293 Cells HeLa Cells Humans Lung Neoplasms / drug therapy Lung Neoplasms / genetics* Lung Neoplasms / pathology Male Mice Mice, Inbred BALB C Mice, Nude Middle Aged Molecular Targeted Therapy* RNA, Small Interfering / pharmacology RNA, Small Interfering / therapeutic use Tumor Cells, Cultured Xenograft Model Antitumor Assays
IF 7.971
DNA material CSII-CMV-MCS-IRES2-Bsd (RDB04385) CS-RfA-EVBsd (RDB06090) pCMV-VSV-G-RSV-Rev (RDB04393) pCAG-HIVgp (RDB04394)