Abstract Vulvar squamous cell carcinoma (VSCC) is a rare but aggressive malignancy that primarily affects women over the age of 60, with the earliest stages often obscured by vulvar lichen sclerosus (VLS). VLS is commonly treated with ultrapotent corticosteroids such as clobetasol. Our previous studies demonstrated that clobetasol treatment of A431 vulvar cancer cells results in the loss of the cell-cell junction proteins E- and P-cadherin and the subsequent gain of the intermediate filament protein vimentin. The resulting cells (referred to as A431D) do not form adherens junctions nor desmosomes. Loss of E- and P-cadherin and gain of vimentin expression is consistent with an epithelial-to-mesenchymal transition (EMT), a process associated with cancer progression and acquisition of a more aggressive phenotype. Despite these changes, A431D cells retain expression of the epithelial intermediate filaments cytokeratins 8/18. Our analyses revealed colocalization of cytokeratin 8/18 and vimentin within A431D cells. In the absence of cadherin-mediated junctions, the organization of both filament systems, and the overall morphology of the cells, resembles that of fibroblasts. It is only upon exogenous expression of an E-cadherin-plakoglobin construct, that desmosome and adherens junctions form. In the studies presented we tested the hypothesis that vimentin is driving the morphology of the A431D cells in spite of continued cytokeratin 8/18 expression even when E- and P-cadherin or E-plakoglobin were exogenously expressed in these cells. A431D cells were transfected with plasmids containing E-, P-, or a construct of E-plakoglobin and the resulting cells were examined for localization of vimentin and cytokeratin 8/18 by confocal microscopy. Citation Format: Jani E. Lewis, Avinash Gopal, Sara M. Mongelli, Abby R. Stevenson. Morphological effects of cytokeratin 8/18 and vimentin coexpression in vulvar cancer cells abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 4835.
Lewis et al. (2026) studied this question.