Src family kinases mediate betel quid-induced oral cancer cell motility and could be a biomarker for early invasion in oral squamous cell carcinoma

Jeff Yi Fu Chen, Chih Chang Hung, Kai Lieh Huang, Yi Ting Chen, Shyun Yeu Liu, Wei Fan Chiang, Hau Ren Chen, Ching Yu Yen, Yu Jen Wu, Jenq Yuh Ko, Yuh Shan Jou

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Betel quid (BQ)-chewing oral cancer is a prevalent disease in many countries of Southeast Asia. Yet, the precise disease mechanism remains largely unknown. Here, we show that BQ extract-induced cell motility in three oral cancer cells (Ca9-22, SAS, and SCC9) presumably involves the Src family kinases (SFKs). Besides, BQ extract can markedly induce cell migration of wild type mouse embryonic fibroblasts (MEFs) but not MEFs lacking three SFK members, namely, Src, Yes, and Fyn, indicating the requirement of SFKs for BQ-induced cell motility. Betel quid extract can also elevate cellular SFK activities because phosphorylation of tyrosine 416 at the catalytic domain is increased, which in turn promotes phosphorylation of an in vitro substrate, enolase. Furthermore, we identified that areca nut, a major component of BQ, is the key factor accounting for BQ-induced cell migration and invasion through SFKs-mediated signaling pathways. Immunohistochemistry revealed that, particularly in BQ-chewing cases, the activity of SFKs was significantly higher in tumor-adjacent mucosa than that in solid tumor areas (P <.01). These results suggest a possible role of SFKs in tumor-host interface and thus in early tumor invasion in vivo. Consistent with this is the observation that activation of SFKs is colocalized with invasive tumor fronts in oral squamous cell carcinoma. Together, we conclude that SFKs may represent a potential biomarker of invasion and therapeutic target in BQ-induced oral cancer.

Original languageEnglish
Pages (from-to)1393-1401
Number of pages9
JournalNeoplasia (New York, N.Y.)
Volume10
Issue number12
DOIs
Publication statusPublished - Dec 2008
Externally publishedYes

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src-Family Kinases
Mouth Neoplasms
Cell Movement
Squamous Cell Carcinoma
Biomarkers
Mastication
Neoplasms
Fibroblasts
Phosphorylation
Areca
Southeastern Asia
Nuts
Phosphopyruvate Hydratase
Tyrosine
Catalytic Domain
Mucous Membrane
Immunohistochemistry

ASJC Scopus subject areas

  • Cancer Research

Cite this

Src family kinases mediate betel quid-induced oral cancer cell motility and could be a biomarker for early invasion in oral squamous cell carcinoma. / Chen, Jeff Yi Fu; Hung, Chih Chang; Huang, Kai Lieh; Chen, Yi Ting; Liu, Shyun Yeu; Chiang, Wei Fan; Chen, Hau Ren; Yen, Ching Yu; Wu, Yu Jen; Ko, Jenq Yuh; Jou, Yuh Shan.

In: Neoplasia (New York, N.Y.), Vol. 10, No. 12, 12.2008, p. 1393-1401.

Research output: Contribution to journalArticle

Chen, Jeff Yi Fu ; Hung, Chih Chang ; Huang, Kai Lieh ; Chen, Yi Ting ; Liu, Shyun Yeu ; Chiang, Wei Fan ; Chen, Hau Ren ; Yen, Ching Yu ; Wu, Yu Jen ; Ko, Jenq Yuh ; Jou, Yuh Shan. / Src family kinases mediate betel quid-induced oral cancer cell motility and could be a biomarker for early invasion in oral squamous cell carcinoma. In: Neoplasia (New York, N.Y.). 2008 ; Vol. 10, No. 12. pp. 1393-1401.
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AU - Chen, Yi Ting

AU - Liu, Shyun Yeu

AU - Chiang, Wei Fan

AU - Chen, Hau Ren

AU - Yen, Ching Yu

AU - Wu, Yu Jen

AU - Ko, Jenq Yuh

AU - Jou, Yuh Shan

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