Selenophosphate synthetase 2 (SEPHS2) synthesizes selenide and ATP into selenophosphate, the selenium donor for selenocysteine (Sec), which is cotranslationally incorporated into selenoproteins. The action and regulatory mechanisms of SEPHS2 as well as its role in carcinogenesis (especially breast cancer) remain ambiguous and need further clarification. Therefore, lacking an experimentally determined structure for SEPHS2, we first analyzed the physicochemical properties of its sequence, modeled its three-dimensional structure and studied its conformational behavior to identify the key residues (named HUB nodes) responsible for protein stability and to clarify the molecular mechanisms by which it induced its function. Bioinformatics analysis evidenced higher amplification frequencies of SEPHS2 in breast cancer than in other cancer types. Therefore, because triple negative breast cancer (TNBC) is biologically the most aggressive breast cancer subtype and its treatment represents a challenge due to the absence of well-defined molecular targets, we evaluated SEPHS2 expression in two TNBC cell lines and patient samples. We demonstrated mRNA and protein overexpression to be correlated with aggressiveness and malignant tumor grade, suggesting that this protein could potentially be considered a prognostic marker and/or therapeutic target for TNBC.
Phosphotransferases/chemistry , Phosphotransferases/genetics , Selenocysteine/metabolism , Triple Negative Breast Neoplasms/genetics , Amino Acid Sequence , Female , Gene Amplification , Humans , Phosphotransferases/metabolism , Protein Stability , Triple Negative Breast Neoplasms/metabolism , Triple Negative Breast Neoplasms/pathology
Palmoplantar keratoderma (PPK) refers to a genetically heterogeneous group of skin diseases, which may be inherited in autosomal dominant or recessive fashion. We observed a case of a 74-year-old man with Mal de Meleda, who developed malignant melanoma inside the hyperkeratotic palmar skin of the right hand. Many authors have reported a higher incidence of cancer in cases affected by palmoplantar hyperkeratosis both for hereditary association and particularly for mechanical damage of the affected areas. The association with melanoma has already been described, but not in a true Mal de Meleda type syndrome as in the case reported in this paper.
Keratoderma, Palmoplantar/complications , Melanoma/etiology , Skin Neoplasms/etiology , Aged , Humans , Keratoderma, Palmoplantar/genetics , Keratoderma, Palmoplantar/pathology , Male , Melanoma/pathology , Pedigree , Skin Neoplasms/pathology
