Enhancement of leukemia‐like phenotypes in Drosophila mxc mutant larvae due to activation of the RAS‐MAP kinase cascade possibly via down‐regulation of DE‐cadherin. (18th November 2020)

• Record Type: Journal Article
• Authors: Kurihara, Masanori; Takarada, Kazuki; Inoue, Yoshihiro H.
• Is Part Of: Genes to cells. Volume 25:Number 12(2020)
• Page Start: 757
• Page End: 769
• Publication Date: 2020-11-18
• Subjects: Drosophila -- hemocytes -- lymph gland -- MAP kinase -- MCRIP -- MMP1 -- mxc -- Ras; Cytogenetics -- Periodicals; Cells -- Mechanical properties -- Periodicals; Molecular genetics -- Periodicals; Genes -- Periodicals; Molecular biology -- Periodicals; Cytology -- Periodicals; Biomechanics -- Periodicals; 571.6
• DOI: 10.1111/gtc.12811
• Languages: English
• ISSNs: 1356-9597

Abstract

Abstract: Loss of mxc gene function in mature hemocytes of Drosophila mxc mbn1 mutant results in malignant hyperplasia in larval hematopoietic tissues termed lymph glands (LGs) owing to over‐proliferation of immature cells. This is a useful model for genetic analyses of leukemia progression. To identify other mutations that deteriorate the hyperplasia, we aimed to investigate whether hyper‐activation of common signaling cascade enabled to enhance the phenotypes. Ectopic expression of the constitutively active forms of MAPK signaling factors in the mutant increased the hyperplasia and the number of circulating hemocytes, resulting in the production of LG fragments. The LG phenotype was related to the reduced DE‐cadherin level in the mutants. Depletion of Drosophila MCRIP, involved in MAPK‐induced silencing of cadherin gene expression, exhibited a similar enhancement of the mxc mbn1 phenotypes. Furthermore, expression of MMP1 proteinase that cleaves the extracellular matrix proteins increased in the mutant larvae harboring MAPK cascade activation. Depletion of Mmp1 and that of pnt (required for Mmp1 expression) suppressed the LG hyperplasia. Hence, we speculated that reduction in DE‐cadherin level by either down‐regulation of MCRIP or up‐regulation of MMP1 was involved in the progression of the tumor phenotype. Our findings can contribute to understanding the mechanism underlying human leukemia progression. Abstract : The leukemia‐like phenotypes in Drosophila mxc mutant larvae due to activation of the RAS‐MAP kinase cascade possibly via down‐regulation of DE‐cadherin.