The SIGnaling Network
Open Resource

Pathway ID: SIGNOR-LBCView in NDEx

Description: Breast cancer is the most frequently occurring cancer in women in the developed world, with oestrogen receptor (ER)-positive disease representing around two- thirds of all cases. In this model we focus on ER-positive/HER2- negative breast cancer who results from mutations in four main signalling pathways: 1)PI3K/AKT/mTOR pathway; 2)cyclin D1 complex/Rb/E2F pathway; 3)TP53/MDM2 pathway; and 4) FGFR1 pathway. Genes from the PI3K/AKT/mTOR pathway are the most frequently mutated in luminal breast cancer; PI3K mutations are the most prevalent mutations and are identified in around 40% of cases; In luminal tumours, inhibition of the Rb protein is mediated through CCND1 (the gene coding for cyclin D1) or CDK4 amplification or overexpression, or loss of the endogenous CDK inhibitors (CDKN2A), these muatations prevent the inactivation of the E2F transcription factor, thus leading to cell cycle progression from G1 to S phase. The TCGA showed amplification of CCND1 in 29% of patients with luminal A tumours and in 58% of patients with luminal B tumours. Moreover, two-thirds of luminal B tumours may have defective p53 pathways, either through TP53 mutations or MDM2 amplification. Finally, FGFR signalling through FGF ligand dependent or independent activation has been implicated in oncogenesis, angiogenesis and treatment resistance in various tumour types. Indeed, FGFR1 amplification has been found in up to 10% of breast cancer tumours.

Curated by: Livia Perfetto