CD44 interacts with EGFR and promotes head and neck squamous cell carcinoma initiation and progression

Aymee Perez, David M. Neskey, Judy Wen, Lutecia Pereira, Erika P. Reategui, W. Jarrard Goodwin, Kermit L. Carraway, Elizabeth J Franzmann

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Objectives: CD44 is a promising target for therapy in head and neck squamous cell carcinoma (HNSCC) and has two defined roles in tumorigenesis: it is a cancer stem cell (CSC) marker and it promotes migration and proliferation through interaction with many signaling molecules. The purpose of this study was to investigate the role of CD44 in HNSCC carcinogenesis. Materials and methods: The effects of CD44 in cell proliferation, migration, apoptosis and cisplatin resistance were studied by its overexpression in HNSCC cells. We also evaluated the effect of CD44 on tumor progression by siRNA methodology, immunohistochemistry (IHC) and western blot analysis. CD44 and EGFR colocalization were examined in CAL 27 cells by laser scanning confocal microscopy. The interaction between CD44 and EGFR was analyzed by immunoprecipation. Results: Overexpression of CD44 enhances cell proliferation and migration and correlates with increased cisplatin resistance and apoptosis inhibition in SCC25 cells. Downregulation of CD44 in CAL27 cells inhibited constitutive EGFR phosphorylation and significantly reduced tumor growth in nude mice. CD44 and EGFR colocalized in CAL 27 cells. CD44 coimmunoprecipated with EGFR in CAL 27 cells, indicating that these proteins interact with each other. Conclusion: CD44 therapy in HNSCC may target the CSC population and alter EGFR signaling.

Original languageEnglish
Pages (from-to)306-313
Number of pages8
JournalOral Oncology
Volume49
Issue number4
DOIs
StatePublished - Apr 1 2013

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Neoplastic Stem Cells
Cisplatin
Cell Movement
Carcinogenesis
Cell Proliferation
Apoptosis
Nude Mice
Confocal Microscopy
Small Interfering RNA
Carcinoma, squamous cell of head and neck
Neoplasms
Down-Regulation
Western Blotting
Immunohistochemistry
Phosphorylation
Therapeutics
Growth
Population
Proteins

Keywords

  • Cancer stem cells
  • CD44
  • Cell proliferation
  • Head and neck squamous cell carcinoma
  • Treatment resistance

ASJC Scopus subject areas

  • Oncology
  • Oral Surgery
  • Cancer Research

Cite this

CD44 interacts with EGFR and promotes head and neck squamous cell carcinoma initiation and progression. / Perez, Aymee; Neskey, David M.; Wen, Judy; Pereira, Lutecia; Reategui, Erika P.; Goodwin, W. Jarrard; Carraway, Kermit L.; Franzmann, Elizabeth J.

In: Oral Oncology, Vol. 49, No. 4, 01.04.2013, p. 306-313.

Research output: Contribution to journalArticle

Perez, Aymee ; Neskey, David M. ; Wen, Judy ; Pereira, Lutecia ; Reategui, Erika P. ; Goodwin, W. Jarrard ; Carraway, Kermit L. ; Franzmann, Elizabeth J. / CD44 interacts with EGFR and promotes head and neck squamous cell carcinoma initiation and progression. In: Oral Oncology. 2013 ; Vol. 49, No. 4. pp. 306-313.
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