Arl4c expression in colorectal and lung cancers promotes tumorigenesis and may represent a novel therapeutic target

Shinsuke Fujii, S. Matsumoto, S. Nojima, E. Morii, A. Kikuchi

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)4834-4844
Number of pages11
JournalOncogene
Volume34
Issue number37
DOIs
Publication statusPublished - Sep 10 2015
Externally publishedYes

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Colorectal Neoplasms
Lung Neoplasms
Carcinogenesis
Catenins
Neoplasms
Morphogenesis
Small Interfering RNA
ADP-Ribosylation Factors
HCT116 Cells
Therapeutics
Mitogen-Activated Protein Kinases
Epidermal Growth Factor
Epithelial Cells
Cell Proliferation
Messenger RNA
Injections
Growth
Proteins

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cancer Research
  • Genetics
  • Medicine(all)

Cite this

Arl4c expression in colorectal and lung cancers promotes tumorigenesis and may represent a novel therapeutic target. / Fujii, Shinsuke; Matsumoto, S.; Nojima, S.; Morii, E.; Kikuchi, A.

In: Oncogene, Vol. 34, No. 37, 10.09.2015, p. 4834-4844.

Research output: Contribution to journalArticle

Fujii, Shinsuke ; Matsumoto, S. ; Nojima, S. ; Morii, E. ; Kikuchi, A. / Arl4c expression in colorectal and lung cancers promotes tumorigenesis and may represent a novel therapeutic target. In: Oncogene. 2015 ; Vol. 34, No. 37. pp. 4834-4844.
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