Fusions of KIF5B and RET have been identified in a number cases of lung adenocarcinomas (a subtype of non-small-cell lung cancer). RET encodes a cellular tyrosine kinase transmembrane receptor; activation of RET stimulates multiple downstream pathways that promote cell growth, proliferation, survival and differentiation. KIF5B encodes a kinesin heavy chain, one of a family of microtubule-associated motor proteins.
A UAS KIF5B-RET fusion construct, derived from a patient-derived KIF5B-RET cDNA and indicated in FlyBase as Hsap\KIF5B::Hsap\RET, has been introduced into flies. Targeting the fusion gene to epithelial tissues results in multiple aspects of transformation, including hyperproliferation, epithelial-to-mesenchymal transition, and extension of long filopodia-like processes into neighboring regions of wild-type cells. Using a driver expressed in multiple developing structures, expression of the KIF5B-RET fusion results in pupal lethality; this phenotype has been used to characterize genetic interactions, as well as to assess the efficacy of single and combined pharmaceutical interventions.
[updated Mar. 2018 by FlyBase; FBrf0222196]
Lung cancer is the leading cause of cancer deaths in the U.S. and worldwide. The 2 major forms of lung cancer are non-small cell lung cancer and small cell lung cancer, which account for 85% and 15% of all lung cancers, respectively. Non-small cell lung cancer can be divided into 3 major histologic subtypes: squamous cell carcinoma, adenocarcinoma, and large cell lung cancer. [from MIM:211980, 2018.03.19]
RET (rearranged during transfection proto-oncogene) encodes a cellular tyrosine kinase transmembrane receptor. Activation of RET stimulates multiple downstream pathways that promote cell growth, proliferation, survival and differentiation. These pathways include the mitogen-activated protein kinase (MAPK), the phosphoinositide 3-kinase (PI3K) and protein kinase B, signal transducer and activator of transcription 3, proto-oncogene tyrosine-protein kinase Src1 and focal adhesion kinase pathways (Romei et al., 2016; pubmed:26868437).
Many to one: 3 human to 1 Drosophila; additional more distantly related genes in both species.
One to one: 1 human to 1 Drosophila; additional more distantly related genes in both species.
