Abstract
Genes of the Wnt and Frizzled class, expressed in HNSCC tissue and cell lines, have an established role in cell morphogenesis and differentiation, and also they have oncogenic properties. We studied Wnt and Fz genes as potential tumor-associated markers in HNSCC by qPCR. Expression levels of Wnt and Fz genes in 22 unique frozen samples from HNSCC were measured. We also assessed possible correlation between the expression levels obtained in cancer samples in relation to clinicopathologic outcome. Wnt-1 was not expressed in the majority of the HNSCC studied, whereas Wnt-5A was the most strongly expressed by the malignant tumors. Wnt-10B expression levels were related with higher grade of undifferentiation. Related to Fz genes, Fz-5 showed more expression levels in no-affectation of regional lymph nodes. Kaplan-Meier survival analyses suggest a reduced time of survival for low and high expression of Wnt-7A and Fz-5 mRNA, respectively. qPCR demonstrated that HNSCC express Wnt and Fz members, and suggested that Wnt and Fz signaling is activated in HNSCC cells.
Highlights
Squamous cell carcinoma (SCC) is the most frequent malignant tumor of the head and neck area
The results revealed that Wnt-5A was the most strongly expressed by the central tumor tissues, but Wnt-1 was not expressed in the majority of the head and neck squamous cell carcinomas (HNSCC) studied
Rhee et al [14] observed that Wnt-1 was one of the most expressed in HNSCC cell lines besides Wnt-10B and Wnt-5A
Summary
Squamous cell carcinoma (SCC) is the most frequent malignant tumor of the head and neck area. The diverse receptor–ligand pairs of the Wnt and Frizzled families play essential roles in the regulation of the cell growth, motility, and differentiation during embryonic development [1, 2]. Genes of the wingless (Wnt) and frizzled (Fz) class have an established role in cell morphogenesis and cellular differentiation [3,4,5]. Wnt genes encode a large family of secreted glycoproteins expressed in species ranging from Drosophila to human. The Wnt glycoproteins are ligands for the Fz receptors, which exert their effects through activation of distinct intracellular signaling pathways. The intracellular Wnt signaling have been recognized in four distinct branches: the canonical β-catenin pathway, which activates the target genes in the nucleus; the planar cell polarity pathway, which involves JNK (Jun N-terminal kinase) and cytoskeletal rearrangements; the Wnt/Ca2+ pathway, which involves activation of PLC (phospholipase C) and PKC (protein kinase); and a pathway that regulates spindle orientation and asymmetric cell division [6,7,8,9,10]
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