Targeting L1 cell adhesion molecule using lentivirus-mediated short hairpin RNA interference reverses aggressiveness of oral squamous cell carcinoma

Shiao Chen Hung, I. Hui Wu, Shui Sang Hsue, Chia Hui Liao, Hsien Chi Wang, Pei Hsin Chuang, Shian Ying Sung, Chia Ling Hsieh

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

The L1 cell adhesion molecule (L1CAM) has been implicated in tumor progression of many types of cancers, but its role in oral squamous cell carcinoma (OSCC) has not been investigated. In the present study, we demonstrated overexpression of L1CAM in OSCC cells, but not in normal keratinocytes, using both clinical specimens and cell lines. This overexpression demonstrated a strong correlation with less differentiation and a higher invasion potential of cancer cells, supporting the significance of L1CAM in human OSCC tumor progression. Targeting L1CAM gene expression in SCC4 cells overexpressing L1CAM using a lentivirus-mediated small hairpin RNA (shRNA) led to a significant reduction in cell proliferation in vitro via retardation of cell cycle at the G1 phase. In addition, shRNA knockdown of L1CAM strongly attenuated the migration and invasion of SCC4 cells, and this was also observed to parallel increased E-cadherin levels and decreased levels of vimentin, fibronectin, and Snail-family transcription factors, indicating that L1CAM expression was related to the epithelial-mesenchymal transition. Furthermore, while mice receiving orthotopically placed control SCC4 cells died within 40 days due to invasive tumor growth and regional lymph node metastasis, prolonged animal survival and complete suppression of tumor progression was observed in mice implanted with L1CAM-deficent SCC4 cells, further substantiating the fundamental importance of L1CAM in OSCC pathophysiology. Our findings suggested that L1CAM is a critical mediator of tumor progression in OSCC, and targeting L1CAM using lentivirus-mediated shRNA may be a useful molecular pharmaceutical approach for the treatment of advanced OSCC.

Original languageEnglish
Pages (from-to)2312-2323
Number of pages12
JournalMolecular Pharmaceutics
Volume7
Issue number6
DOIs
Publication statusPublished - Dec 6 2010
Externally publishedYes

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Neural Cell Adhesion Molecule L1
Lentivirus
RNA Interference
Small Interfering RNA
Squamous Cell Carcinoma
Neoplasms
Epithelial-Mesenchymal Transition
G1 Phase
Vimentin
Cadherins
Keratinocytes
Fibronectins
Cell Cycle

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Molecular Medicine
  • Drug Discovery

Cite this

Targeting L1 cell adhesion molecule using lentivirus-mediated short hairpin RNA interference reverses aggressiveness of oral squamous cell carcinoma. / Hung, Shiao Chen; Wu, I. Hui; Hsue, Shui Sang; Liao, Chia Hui; Wang, Hsien Chi; Chuang, Pei Hsin; Sung, Shian Ying; Hsieh, Chia Ling.

In: Molecular Pharmaceutics, Vol. 7, No. 6, 06.12.2010, p. 2312-2323.

Research output: Contribution to journalArticle

Hung, Shiao Chen ; Wu, I. Hui ; Hsue, Shui Sang ; Liao, Chia Hui ; Wang, Hsien Chi ; Chuang, Pei Hsin ; Sung, Shian Ying ; Hsieh, Chia Ling. / Targeting L1 cell adhesion molecule using lentivirus-mediated short hairpin RNA interference reverses aggressiveness of oral squamous cell carcinoma. In: Molecular Pharmaceutics. 2010 ; Vol. 7, No. 6. pp. 2312-2323.
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