Deleted in breast cancer 1 (DBC1) deficiency results in apoptosis of breast cancer cells through impaired responses to UV-induced DNA damage

Kim, Wootae; Kim, Ja-Eun

doi:10.1016/j.canlet.2013.01.026

Cited by 24 publications

(21 citation statements)

References 42 publications

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“…Therefore, DBC1 inhibition in combination with conventional anti-cancer therapy might be effective. Especially, in situations where the DBC1-SIRT1 interaction is weak, the depletion of DBC1 induced breast cancer cell death in response to ultraviolet irradiation [54]. Accordingly, the application of DBC1-targetted therapy could be applicable in cancers where the SIRT1-DBC1 interaction has been deregulated.…”

Section: Discussionmentioning

confidence: 99%

Expression of SIRT1 and DBC1 Is Associated with Poor Prognosis of Soft Tissue Sarcomas

et al. 2013

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Recently, the roles of SIRT1 and deleted in breast cancer 1 (DBC1) in human cancer have been extensively studied and it has been demonstrated that they are involved in many human carcinomas. However, their clinical significance for soft-tissue sarcomas has not been examined. In this study, we evaluated the expression and prognostic significance of the expression of SIRT1, DBC1, P53, β-catenin, cyclin D1, and KI67 in 104 cases of soft-tissue sarcomas. RESULTS: Immunohistochemical expression of SIRT1, DBC1, P53, β-catenin, and cyclin D1 were seen in 71%, 74%, 53%, 48%, and 73% of sarcomas, respectively. The expression of SIRT1, DBC1, P53, β-catenin, and cyclin D1 were significantly correlated with advanced clinicopathological parameters such as higher clinical stage, higher histological grade, increased mitotic counts, and distant metastasis. The expression of SIRT1, DBC1, P53, β-catenin, cyclin D1, and KI67 were significantly correlated with each other and positive expression of all of these predicted shorter overall survival and event-free survival by univariate analysis. Multivariate analysis revealed the expression of SIRT1 as an independent prognostic indicator for overall survival and event-free survival of sarcoma patients. In conclusion, this study demonstrates that SIRT1- and DBC1-related pathways may be involved in the progression of soft-tissue sarcomas and can be used as clinically significant prognostic indicators for sarcoma patients. Moreover, the SIRT1- and DBC1-related pathways could be new therapeutic targets for the treatment of sarcomas.

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Section: Discussionmentioning

confidence: 99%

Expression of SIRT1 and DBC1 Is Associated with Poor Prognosis of Soft Tissue Sarcomas

et al. 2013

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“…This phenomenon might be ascribed to different experimental conditions, which can result in different effects of DBC1 depletion. Indeed, recently, other papers reported that DBC1 absence, in response to various stimuli, enhances cell death (43–45), thus supporting a model in which DBC1 can modulate apoptosis depending on the cellular context, type of damage and on the duration of genotoxic stress.…”

Section: Discussionmentioning

confidence: 73%

Chk2 and REGγ-dependent DBC1 regulation in DNA damage induced apoptosis

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Ruscica

Buscemi

et al. 2014

Nucleic Acids Research

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Human DBC1 (Deleted in Breast Cancer 1; KIAA1967; CCAR2) is a protein implicated in the regulation of apoptosis, transcription and histone modifications. Upon DNA damage, DBC1 is phosphorylated by ATM/ATR on Thr454 and this modification increases its inhibitory interaction with SIRT1, leading to p53 acetylation and p53-dependent apoptosis. Here, we report that the inhibition of SIRT1 by DBC1 in the DNA damage response (DDR) also depends on Chk2, the transducer kinase that is activated by ATM upon DNA lesions and contributes to the spreading of DNA damage signal. Indeed we found that inactivation of Chk2 reduces DBC1-SIRT1 binding, thus preventing p53 acetylation and DBC1-induced apoptosis. These events are mediated by Chk2 phosphorylation of the 11S proteasome activator REGγ on Ser247, which increases REGγ-DBC1 interaction and SIRT1 inhibition. Overall our results clarify the mechanisms underlying the DBC1-dependent SIRT1 inhibition and link, for the first time, Chk2 and REGγ to the ATM-DBC1-SIRT1 axis.

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“…This study reported that a loss of DBC1 led to a failure in activating the DNA damage checkpoint and JNK pathway for cell survival, following UV-induced DNA damage. These findings suggest that DBC1 promotes genome stability in response to DNA damage, albeit in a SIRT1-independent manner [39].…”

Section: Dbc1 Is a Mediator Of Cellular Responses To Stressmentioning

confidence: 81%

“…Breast cancer Increased [39,[45][46][47][48] Colorectal cancer Increased [50] Esophageal squamous cell carcinoma (ESCC) Increased [49] Gastric carcinoma Increased [54] Lung adenocarcinoma (Lung AD) Increased [55] Liver human hepatocellular carcinoma (HCC) Increased [51] Prostate cancer No change [26] Breast cancer Decreased [18] Lung squamous cell carcinoma (Lung SCC) Decreased [55] Pancreatic Ductal Adenocarcinoma (PDAC) Decreased [52] at defining the roles of DBC1. Such approaches may also involve chemoproteomic studies.…”

Section: Cancer Type Dbc1 Expression Referencesmentioning

confidence: 99%