Caveolin-1 overexpression is associated with simultaneous abnormal expression of the E-cadherin/α-β catenins complex and multiple ErbB receptors and with lymph nodes metastasis in head and neck squamous cell carcinomas.
The presence of lymph node metastases is one of the most important prognostic indicators in head and neck squamous cell carcinomas (HNSCCs). An alteration of the E-cadherin-catenins complex and EGFR is essential for the invasiveness of cancer cells. Caveolin-1, the major structural protein of the caveolae, represents a scaffolding molecule for several signaling proteins including EGFR. Although caveolin-1 has been shown to play a role in inducing the invasive phenotype of cancer cells, its role appears to be cell-type specific and for some tumors it has not been defined yet. In this study we used 57 HNSCC specimens to investigate whether the abnormal expression of caveolin-1 was associated with the derangement of the E-cadherin-catenins complex and with the overexpression of ErbB receptors. We demonstrate that in HNSCCs caveolin-1 overexpression is associated with the simultaneous abnormal expression of at least one member of the E-cadherin/α-β catenins complex and multiple ErbB receptors as well as with lymph node metastases. We also demonstrate that chronic stimulation of a human hypopharyngeal carcinoma cell line (FaDu) with EGF induced the internalization of β-catenin and caveolin-1 and their co-localization with EGFR. Moreover, EGF treatment induced an increased physical interaction between EGFR/β-catenin/caveolin-1 and between E-cadherin/β-catenin/caveolin-1. These molecular events were associated with an increased directional motility of FaDu cells in vitro. These findings may provide new insight into the biology of HNSCC progression and help to identify subgroups of primary HNSCCs with a more aggressive behavior.
Department of Experimental Medicine, University Sapienza, Rome, Italy.
Laura
L
Masuelli
Alfredo
A
Budillon
Laura
L
Marzocchella
Marie-Agnes
MA
Mrozek
Domenico
D
Vitolo
Elena
E
Di Gennaro
Simona
S
Losito
Patrizio
P
Sale
Francesco
F
Longo
Franco
F
Ionna
Florigio
F
Lista
Raffaella
R
Muraro
Andrea
A
Modesti
Roberto
R
Bei
D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051242:Caveolin 1 / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000008:administration & dosage*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006258:Head and Neck Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007012:Hypopharyngeal Neoplasms / Q000378:metabolism; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology; D009361:Neoplasm Invasiveness / Q000235:genetics; D009362:Neoplasm Metastasis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D051178:alpha Catenin / Q000235:genetics / Q000378:metabolism; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
D015820:Cadherins; D051242:Caveolin 1; D004815:Epidermal Growth Factor; D018719:Erb-b2 Receptor Tyrosine Kinases; D051178:alpha Catenin; D051176:beta Catenin; C495270:CTNNB1 protein, human