Galectins and Carcinogenesis: Their Role in Head and Neck Carcinomas and Thyroid Carcinomas

Abstract

Head and neck cancers are among the most frequently occurring cancers worldwide. Of the molecular drivers described for these tumors, galectins play an important role via their interaction with several intracellular pathways. In this review, we will detail and discuss this role with specific reference to galectins-1, -3, and -7 in angiogenesis, cell proliferation, and invasion as well as in cell transformation and cancer progression. Furthermore, we will evaluate the prognostic value of galectin expression in head and neck cancers including those with oral cavity, salivary gland, and nasopharyngeal pathologies. In addition, we will discuss the involvement of these galectins in thyroid cancers where their altered expression is proposed as a new diagnostic biomarker.

Keywords: galectins; head and neck cancer; thyroid cancer.

Figure 1

Hallmark of galectins in head and neck cancers. Gal-1, -3, -7, -8, and -9 in cancer progression affecting several pathways including proliferation, apoptosis, invasion, angiogenesis, and tumor-immune escape. Matrix Metalloproteinase (MMP); Interleukin (IL); Focal adhesion kinsase (FAK).

Figure 2

Alterations of galectin-1, -3, -7, -8, and -9 genes in head and neck squamous cell carcinoma (A) and thyroid cancer (B). Molecular alterations were investigated with the cBioPortal for Cancer Genomics [15], evaluating RNA expression, copy number variation, and mutation using The Cancer Genome Atlas (TCGA) datasets. Alteration events are displayed by samples ((A), n = 279; (B), n = 507).

Figure 3

Involvement of galectins during carcinogenesis. Gal-1 interacts with Neuropilin-1/Vascular endothelial growth factor-2 (NPR-1/VEGFR-2) complex to promote endothelial cells migration through the c-Jun N-terminal kinase (JNK) pathway. Also, gal-1 interacts with H-Ras to stimulate cell proliferation by the stimulation of the Extracellular signal-regulated kinase (ERK) pathway. Gal-3 promotes cell proliferation and cell migration by the activation of β-catenin through the Phosphoinositide 3-kinase (PI3K)/Akt pathway, but also through Ras homolog family member A (RhoA) signaling. Glycogen synthase kinase 3β (GSK3β); Adenomatous polyposis coli (APC).