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CTC1 increases the radioresistance of human melanoma cells by inhibiting telomere shortening and apoptosis. 2014

Y M Luo, and N X Xia, and L Yang, and Z Li, and H Yang, and H J Yu, and Y Liu, and H Lei, and F X Zhou, and C H Xie, and Y F Zhou
Hubei Cancer Clinical Study Center, Hubei Key Laboratory of Tumor Biological Behaviors, Wuhan University, Wuhan, Hubei, P.R. China.

Melanoma has traditionally been viewed as a radioresistant cancer. However, recent studies suggest that under certain clinical circumstances, radiotherapy may play a significant role in the treatment of melanoma. Previous studies have demonstrated that telomere length is a hallmark of radiosensitivity. The newly discovered mammalian CTC1‑STN1-TEN1 (CST) complex has been demonstrated to be an important telomere maintenance factor. In this study, by establishing a radiosensitive/radioresistant human melanoma cell model, MDA-MB-435/MDA-MB‑435R, we aimed to investigate the association of CTC1 expression with radiosensitivity in human melanoma cell lines, and to elucidate the possible underlying mechanisms. We found that CTC1 mRNA and protein levels were markedly increased in the MDA-MB‑435R cells compared with the MDA-MB‑435 cells. Moreover, the downregulation of CTC1 enhanced radiosensitivity, induced DNA damage and promoted telomere shortening and apoptosis in both cell lines. Taken together, our findings suggest that CTC1 increases the radioresistance of human melanoma cells by inhibiting telomere shortening and apoptosis. Thus, CTC1 may be an attractive target gene for the treatment of human melanoma.

UI MeSH Term Description Entries
D008545 Melanoma A malignant neoplasm derived from cells that are capable of forming melanin, which may occur in the skin of any part of the body, in the eye, or, rarely, in the mucous membranes of the genitalia, anus, oral cavity, or other sites. It occurs mostly in adults and may originate de novo or from a pigmented nevus or malignant lentigo. Melanomas frequently metastasize widely, and the regional lymph nodes, liver, lungs, and brain are likely to be involved. The incidence of malignant skin melanomas is rising rapidly in all parts of the world. (Stedman, 25th ed; from Rook et al., Textbook of Dermatology, 4th ed, p2445) Malignant Melanoma,Malignant Melanomas,Melanoma, Malignant,Melanomas,Melanomas, Malignant
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D016615 Telomere A terminal section of a chromosome which has a specialized structure and which is involved in chromosomal replication and stability. Its length is believed to be a few hundred base pairs. Telomeres
D017209 Apoptosis A regulated cell death mechanism characterized by distinctive morphologic changes in the nucleus and cytoplasm, including the endonucleolytic cleavage of genomic DNA, at regularly spaced, internucleosomal sites, i.e., DNA FRAGMENTATION. It is genetically programmed and serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. Apoptosis, Extrinsic Pathway,Apoptosis, Intrinsic Pathway,Caspase-Dependent Apoptosis,Classic Apoptosis,Classical Apoptosis,Programmed Cell Death,Programmed Cell Death, Type I,Apoptoses, Extrinsic Pathway,Apoptoses, Intrinsic Pathway,Apoptosis, Caspase-Dependent,Apoptosis, Classic,Apoptosis, Classical,Caspase Dependent Apoptosis,Cell Death, Programmed,Classic Apoptoses,Extrinsic Pathway Apoptoses,Extrinsic Pathway Apoptosis,Intrinsic Pathway Apoptoses,Intrinsic Pathway Apoptosis
D045744 Cell Line, Tumor A cell line derived from cultured tumor cells. Tumor Cell Line,Cell Lines, Tumor,Line, Tumor Cell,Lines, Tumor Cell,Tumor Cell Lines
D053903 DNA Breaks, Double-Stranded Interruptions in the sugar-phosphate backbone of DNA, across both strands adjacently. Double-Stranded DNA Breaks,Double-Strand DNA Breaks,Double-Stranded DNA Break,Break, Double-Strand DNA,Break, Double-Stranded DNA,Breaks, Double-Strand DNA,Breaks, Double-Stranded DNA,DNA Break, Double-Strand,DNA Break, Double-Stranded,DNA Breaks, Double Stranded,DNA Breaks, Double-Strand,Double Strand DNA Breaks,Double Stranded DNA Break,Double Stranded DNA Breaks,Double-Strand DNA Break
D059506 Telomere Shortening The loss of some TELOMERE sequence during DNA REPLICATION of the first several base pairs of a linear DNA molecule; or from DNA DAMAGE. Cells have various mechanisms to restore length (TELOMERE HOMEOSTASIS.) Telomere shortening is involved in the progression of CELL AGING. Shortening, Telomere,Shortenings, Telomere,Telomere Shortenings
D034501 Telomere-Binding Proteins Proteins that specifically bind to TELOMERES. Proteins in this class include those that perform functions such as telomere capping, telomere maintenance and telomere stabilization. Telomere-Binding Protein,Double-Stranded Telomere-Binding Proteins,Double-Stranded Telomeric Binding Protein,Single-Stranded Telomere-Binding Protein,Single-Stranded Telomere-Binding Proteins,Telomer-Binding Protein, alpha-Subunit,Telomer-Binding Protein, beta-Subunit,Telomere End-Binding Protein (TEBP),Telomere Repeat Binding Factor,Telomere Repeat Binding Factors,Telomere Repeat Binding Proteins,Telomere-Binding Proteins, Double Stranded,Telomere-Binding Proteins, Single-Stranded,alpha-Telomere-Binding Protein,beta-Telomere-Binding Protein,Double Stranded Telomere Binding Proteins,Double Stranded Telomeric Binding Protein,Protein, Telomere-Binding,Single Stranded Telomere Binding Protein,Single Stranded Telomere Binding Proteins,Telomer Binding Protein, alpha Subunit,Telomer Binding Protein, beta Subunit,Telomere Binding Protein,Telomere Binding Proteins,Telomere Binding Proteins, Double Stranded,Telomere Binding Proteins, Single Stranded,Telomere-Binding Protein, Single-Stranded,Telomere-Binding Proteins, Double-Stranded,alpha Telomere Binding Protein,alpha-Subunit Telomer-Binding Protein,beta Telomere Binding Protein,beta-Subunit Telomer-Binding Protein

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