Human Gene Set: PEDERSEN_TARGETS_OF_611CTF_ISOFORM_OF_ERBB2


Standard name PEDERSEN_TARGETS_OF_611CTF_ISOFORM_OF_ERBB2
Systematic name M2414
Brief description Genes up-regulated in MCF7 cells (breast cancer) more than three-fold by the truncated form 611-CTF of ERBB2 [GeneID=2064] and less than two-fold by the full-length ERBB2 [GeneID=2064].
Full description or abstract HER2 is a tyrosine kinase receptor causally involved in cancer. A subgroup of breast cancer patients with particularly poor clinical outcomes expresses a heterogeneous collection of HER2 carboxy-terminal fragments (CTFs). However, since the CTFs lack the extracellular domain that drives dimerization and subsequent activation of full-length HER2, they are in principle expected to be inactive. Here we show that at low expression levels one of these fragments, 611-CTF, activated multiple signaling pathways because of its unanticipated ability to constitutively homodimerize. A transcriptomic analysis revealed that 611-CTF specifically controlled the expression of genes that we found to be correlated with poor prognosis in breast cancer. Among the 611-CTF-regulated genes were several that have previously been linked to metastasis, including those for MET, EPHA2, matrix metalloproteinase 1, interleukin 11, angiopoietin-like 4, and different integrins. It is thought that transgenic mice overexpressing HER2 in the mammary glands develop tumors only after acquisition of activating mutations in the transgene. In contrast, we show that expression of 611-CTF led to development of aggressive and invasive mammary tumors without the need for mutations. These results demonstrate that 611-CTF is a potent oncogene capable of promoting mammary tumor progression and metastasis.
Collection C2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 19364815   Authors: Pedersen K,Angelini PD,Laos S,Bach-Faig A,Cunningham MP,Ferrer-Ramón C,Luque-García A,García-Castillo J,Parra-Palau JL,Scaltriti M,Ramón y Cajal S,Baselga J,Arribas J
Exact source Fig. 11S
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Source species Homo sapiens
Contributed by Arthur Liberzon (MSigDB Team)
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identifier namespace		 HUMAN_GENE_SYMBOL
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