Intracellular claudin‐1 at the invasive front of tongue squamous cell carcinoma is associated with lymph node metastasis

Abstract

This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. AbstractClaudins are the major component of tight junctions, which form a primary barrier to paracellular diffusion and maintain cell polarity in normal epithelia and endothelia. In cancer cells, claudins play additional roles besides serving as components of the tight junctions, and participate in anoikis or invasion. Among the claudin family proteins, claudin-1 has the most promising potential, both diagnostically and prognostically, in many types of cancers, including oral, gastric, liver, and colon cancers.However, conflicting results have been reported in relation to the degree of claudin-1 expression and the prognosis, suggesting that the expression level of claudin-1 alone is not sufficient to analyze the relationship between claudin-1 and cancer progression. As endocytic trafficking of claudin-1 has been reported in several epithelial cell types in vitro, we aimed to determine whether intracellular localization of claudin-1 is the missing aspect between claudin-1 and cancer. We investigated the expression of claudin-1 in 83 tongue squamous cell carcinoma (TSCC) pathological specimens.Although the expression level of claudin-1 based on immunohistochemistry was not associated with TSCC progression, within the high claudin-1 expression group, the incidence of intracellular localization of claudin-1 was correlated with cervical lymph node metastasis. In an in vitro experiment, claudin-1 was constitutively internalized in TSCC-derived cells. Motility of TSCC-derived cells was increased by deficiency of claudin-1, suggesting that the decrease in cell-surface claudin-1 promoted the cell migration. Therefore, intracellular localization of claudin-1 at the invasion front may represent a promising diagnostic marker of TSCC. K E Y W O R D Sclaudin-1, endocytosis, invasion front, metastasis, tongue squamous cell carcinoma

CLDN15 is a novel diagnostic marker for malignant pleural mesothelioma

“…2 c). A similar change in claudin localization has been reported for CLDN1 in breast cancer, colon cancer and tongue carcinoma; the localization of CLDN1 changes from the membrane to the cytoplasm as the malignancy progresses 28 , 29 .…”

Reduced Claudin-12 Expression Predicts Poor Prognosis in Cervical Cancer

“…Moreover, in colorectal cancer and uterine cervical SCC tissues, CLDN12 was localized in the cytoplasm. Although we do not know why CLDN12 possesses distinct subcellular localization as described above, it has been reported that the CLDN1 localization is altered from cell membranes to cytoplasm at the invasion front of tongue SCC tissues [ 36 ].…”

Context-Dependent Roles of Claudins in Tumorigenesis

“…Nuclear claudins are mostly found in malignant tissues, suggesting their role in cancer. They are always found in complexes containing other proteins, such as b-catenin, YAP, ZO-1, ZO-1 nucleic acid-binding protein (ZONAB), and cyclin D1, and induce retention of such molecules in the nucleus to enhance cell proliferation and cancer progression (48)(49)(50)(51)(52). The underlying mechanisms contributing to their translocation are not well understood but may involve phosphorylation by protein kinases (53).…”