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

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.

Histone Methyltransferase G9a Drives Chemotherapy Resistance by Regulating the Glutamate–Cysteine Ligase Catalytic Subunit in Head and Neck Squamous Cell Carcinoma

“…Chemotherapy resistance is one characteristic of stem-like cancer cells, including in HNSCC (27,28). We observed that our established cisplatin-resistant HNSCC cells with increased G9a also possess more stemness properties than their parental cells.…”

“…Studies have shown that stem-like cancer cells have more ability to resist chemotherapy, including cisplatin (27,28). Thus, we examined whether G9a also contributes to cisplatin resistance in stem-like cancer cells.…”

Discovery of genes from feces correlated with colorectal cancer progression

“…This result may be associated with another marker, CD44, which was detected in the feces of CRC patients at AJCC stage I. CD44 is of functional importance for tumor initiation and progression in CRC (58). In another animal study, downregulated CD44 was able to reduce tumor growth significantly (59). Recently, CD44 was further proposed to contribute to targeted therapeutic strategies due to its role in sensing the extracellular environment (60).…”

Identification of Cancer Stem Cells in Oral Squamous Cell Carcinoma Using Cripto-1.

“…OSCC is still considered the most common malignancy of the oral cavity and the most lethal cancer due to the late detection of this cancer in its advanced stages despite the easy accessibility of the oral cavity for regular examinations (Perez et al, 2013). Several markers were discovered to correlate the relation between this cancer and CSCs and the role of these cells in tumor aggressiveness, such as CD44 and CD109 (Hema et al, 2014).…”