Cooperation of the BTB-Zinc finger protein, Abrupt, with cytoskeletal regulators in Drosophila epithelial tumorigenesis
journal contributionposted on 18.01.2021, 02:14 by N Turkel, Marta Portela-EstebanMarta Portela-Esteban, C Poon, J Li, AM Brumby, Helena RichardsonHelena Richardson
© 2015. Published by The Company of Biologists Ltd. The deregulation of cell polarity or cytoskeletal regulators is a common occurrence in human epithelial cancers. Moreover, there is accumulating evidence in human epithelial cancer that BTB-ZF genes, such as Bcl6 and ZBTB7A, are oncogenic. From our previous studies in the vinegar fly, Drosophila melanogaster, we have identified a cooperative interaction between a mutation in the apico-basal cell polarity regulator Scribble (Scrib) and overexpression of the BTB-ZF protein Abrupt (Ab). Herein, we show that co-expression of ab with actin cytoskeletal regulators, RhoGEF2 or Src64B, in the developing eye-antennal epithelial tissue results in the formation of overgrown amorphous tumours, whereas ab and DRac1 co-expression leadsto non-cell autonomous overgrowth. Together with ab, these genes affect the expression of differentiation genes, resulting in tumours locked in a progenitor cell fate. Finally, we show that the expression of two mammalian genes related to ab, Bcl6 and ZBTB7A, which are oncogenes in mammalian epithelial cancers, significantly correlate with the upregulation of cytoskeletal genes or downregulation of apico-basal cell polarity neoplastic tumour suppressor genes in colorectal, lung and other human epithelial cancers. Altogether, this analysis has revealed that upregulation of cytoskeletal regulators cooperate with Abrupt in Drosophila epithelial tumorigenesis, and that high expression of human BTB-ZF genes, Bcl6 and ZBTB7A, shows significant correlations with cytoskeletal and cell polarity gene expression in specific epithelial tumour types. This highlights the need for further investigation of the cooperation between these genes in mammalian systems.
H.E.R. is supported by a Senior Research Fellowship from the National Health and Medical Research Council (NHMRC) Australia, M.P. from funding from the Cancer Council Victoria Australia, and C.P. was supported by an Australian Postgraduate Award. This work was supported by grants from the NHMRC, #400211 to H.E.R. and A.M.B., and #509051 to A.M.B., and Peter Mac Internal funds to H.E.R.
Pagination16p. (p. 1024-1039)
PublisherCompany of Biologists: OAJ
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Science & TechnologyLife Sciences & BiomedicineBiologyLife Sciences & Biomedicine - Other TopicsDrosophilaEye-antennal discApico-basal cell polarityActin cytoskeletal regulatorsBTB-ZFAbruptRhoGEF2Rac1SrcScribbleCELL-SHAPE CHANGESECTOPIC EYE DEVELOPMENTACTIN-CAPPING PROTEINTUMOR-SUPPRESSORJNK ACTIVATIONHIPPO PATHWAYRHO-GTPASESSIGNALING PATHWAYTISSUE OVERGROWTHPROSTATE-CANCER