title: The role of genes co-amplified with nicastrin in breast invasive carcinoma.
abstract: Breast cancer accounts for more than 450,000 deaths per year worldwide. Discovery of novel therapeutic targets that will allow patient-tailored treatment of this disease is an emerging area of scientific interest. Recently, nicastrin has been identified as one such therapeutic target. Its overexpression is indicative of worse overall survival in the estrogen-receptor-negative patient population. In this paper, we analyze data from a large invasive breast carcinoma study and confirm nicastrin amplification. In search for genes that are co-amplified with nicastrin, we identify a potential novel breast cancer-related amplicon located on chromosome 1. Furthermore, we search for "influential interactors," i.e., genes that interact with a statistically significantly high number of genes which are co-amplified with nicastrin, and confirm their involvement in this female neoplasm. Among the influential interactors, we find genes which belong to the core diseasome (a recently identified therapeutically relevant set of genes which is known to drive disease formation) and propose that they might be important for breast cancer onset, and serve as its novel therapeutic targets. Finally, we identify a pathway that may play a role in nicastrin's amplification process and we experimentally confirm downstream signaling mechanism of nicastrin in breast cancer cells.
authors: Department of Computing, Imperial College London, 180 Queen's Gate, Room 407 Huxley, London, SW7 2AZ, UK.
authors: A
authors: A
authors: Sarajlić
authors: A
authors: A
authors: Filipović
authors: V
authors: V
authors: Janjić
authors: R C
authors: RC
authors: Coombes
authors: N
authors: N
authors: Pržulj
mesh_terms: D053829:Amyloid Precursor Protein Secretases / Q000235:genetics*; D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics*; D018270:Carcinoma, Ductal, Breast / Q000235:genetics*; D045744:Cell Line, Tumor; D005260:Female; D005784:Gene Amplification / Q000235:genetics*; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D060066:Protein Interaction Maps / Q000235:genetics; D055765:Shc Signaling Adaptor Proteins / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D014183:Transplantation, Heterologous
chemical_list: D008562:Membrane Glycoproteins; C528024:SHC1 protein, human; D055765:Shc Signaling Adaptor Proteins; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; C413604:nicastrin protein; D053829:Amyloid Precursor Protein Secretases