The role of X-box binding protein-1 in tumorigenicity. 2009

Ayesha N Shajahan, and Rebecca B Riggins, and Robert Clarke
Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, D.C., USA.

Rapid growth of a tumor can overwhelm the vasculature that supplies it with nutrients and oxygen. Inside such tumors, cells undergo endoplasmic reticulum stress but can survive such adverse microenvironments by an adaptive mechanism called the unfolded protein response (UPR). X-box binding protein-1 (XBP-1) is a critical transcriptional activator of the UPR and is responsible for regulating the function of genes in cell survival. An unconventional splicing of the XBP-1(U) messenger RNA (mRNA) results in two proteins: XBP-1(S) that is often increased in a variety of human cancers and any translated proteins from the unspliced XBP-1(U) mRNA that acts as a dominant negative of endogenous XBP-1(S) action. In cancer cells, overexpression of XBP-1 can confer drug resistance by preventing drug-induced cell-cycle arrest and mitochondrial permeability and apoptosis, while downregulation of XBP-1 increases the sensitivity to killing by hypoxia. XBP-1 is also implicated in cellular de-differentiation, oncovirus infection and the epithelial-to-mesenchymal transition. Given that XBP-1 mediates a wide range of responses in tumorigenesis, it is logical to focus on XBP-1 as an anticancer therapeutic target. Furthermore, combining inhibitors of XBP-1 with other anti-UPR drugs may enhance the activity of some antineoplastic therapies.

UI MeSH Term Description Entries
D009369 Neoplasms New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms. Benign Neoplasm,Cancer,Malignant Neoplasm,Tumor,Tumors,Benign Neoplasms,Malignancy,Malignant Neoplasms,Neoplasia,Neoplasm,Neoplasms, Benign,Cancers,Malignancies,Neoplasias,Neoplasm, Benign,Neoplasm, Malignant,Neoplasms, Malignant
D002470 Cell Survival The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. Cell Viability,Cell Viabilities,Survival, Cell,Viabilities, Cell,Viability, Cell
D004268 DNA-Binding Proteins Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases. DNA Helix Destabilizing Proteins,DNA-Binding Protein,Single-Stranded DNA Binding Proteins,DNA Binding Protein,DNA Single-Stranded Binding Protein,SS DNA BP,Single-Stranded DNA-Binding Protein,Binding Protein, DNA,DNA Binding Proteins,DNA Single Stranded Binding Protein,DNA-Binding Protein, Single-Stranded,Protein, DNA-Binding,Single Stranded DNA Binding Protein,Single Stranded DNA Binding Proteins
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000071701 Regulatory Factor X Transcription Factors A family of eukaryotic transcription factors that recognize and bind to a highly-conserved cis-regulatory sequence (X-box) within the promoter region of MHC CLASS II GENES. They contain a conserved winged-helix DNA binding domain and function as homo or heterodimers. RFX Transcription Factors,Factors, RFX Transcription,Transcription Factors, RFX
D000071717 X-Box Binding Protein 1 A basic leucine zipper transcription factor that regulates expression of MHC CLASS II GENES through its binding to a conserved X-box DNA sequence in the promoter region. It regulates the expression of genes involved in the UNFOLDED PROTEIN RESPONSE. TREB-5 Protein,TREB5 Protein,Tax-Responsive Element-Binding Protein 5,XBP-1 Protein,XBP2 Protein,TREB 5 Protein,Tax Responsive Element Binding Protein 5,X Box Binding Protein 1,XBP 1 Protein
D000970 Antineoplastic Agents Substances that inhibit or prevent the proliferation of NEOPLASMS. Anticancer Agent,Antineoplastic,Antineoplastic Agent,Antineoplastic Drug,Antitumor Agent,Antitumor Drug,Cancer Chemotherapy Agent,Cancer Chemotherapy Drug,Anticancer Agents,Antineoplastic Drugs,Antineoplastics,Antitumor Agents,Antitumor Drugs,Cancer Chemotherapy Agents,Cancer Chemotherapy Drugs,Chemotherapeutic Anticancer Agents,Chemotherapeutic Anticancer Drug,Agent, Anticancer,Agent, Antineoplastic,Agent, Antitumor,Agent, Cancer Chemotherapy,Agents, Anticancer,Agents, Antineoplastic,Agents, Antitumor,Agents, Cancer Chemotherapy,Agents, Chemotherapeutic Anticancer,Chemotherapy Agent, Cancer,Chemotherapy Agents, Cancer,Chemotherapy Drug, Cancer,Chemotherapy Drugs, Cancer,Drug, Antineoplastic,Drug, Antitumor,Drug, Cancer Chemotherapy,Drug, Chemotherapeutic Anticancer,Drugs, Antineoplastic,Drugs, Antitumor,Drugs, Cancer Chemotherapy
D014157 Transcription Factors Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process. Transcription Factor,Factor, Transcription,Factors, Transcription
D016503 Drug Delivery Systems Systems for the delivery of drugs to target sites of pharmacological actions. Technologies employed include those concerning drug preparation, route of administration, site targeting, metabolism, and toxicity. Drug Targeting,Delivery System, Drug,Delivery Systems, Drug,Drug Delivery System,Drug Targetings,System, Drug Delivery,Systems, Drug Delivery,Targeting, Drug,Targetings, Drug
D017510 Protein Folding Processes involved in the formation of TERTIARY PROTEIN STRUCTURE. Protein Folding, Globular,Folding, Globular Protein,Folding, Protein,Foldings, Globular Protein,Foldings, Protein,Globular Protein Folding,Globular Protein Foldings,Protein Foldings,Protein Foldings, Globular

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