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Biology subjects

Zurlo, G.

Publications and source records attributed to Zurlo, G..

2 recordsLinked to original sources

Growth anisotropy of the extracellular matrix drives mechanics in a developing organ

The final size and shape of organs results from volume expansion by growth and shape changes by contractility. Complex morphologies arise from differences in growth rate between tissues. We address here how differential growth drives epithelial thickening and doming during the morphogenesis of the growing Drosophila wing imaginal disc. We report that 3D morphology results from elastic deformation due to differential growth between the epithelial cell layer and its enveloping extracellular matrix (ECM). Furthermore, the ECM envelope exhibits differential growth anisotropy (i.e. anisotropic expansion in 3D), growing in-plane on one side, but out of plane on the other side. The elasticity, anisotropy and morphogenesis is fully captured by a mechanical bilayer model. Moreover, differential expression of the Matrix metalloproteinase MMP2 controls growth anisotropy of the two ECM layers. This study shows that the ECM is a controllable mechanical constraint whose intrinsic growth anisotropy directs tissue morphogenesis in a developing organ.

developmental biology↗

ZHX2 Promotes HIF1α Oncogenic Signaling in Triple-Negative Breast Cancer

Triple-negative breast cancer (TNBC) is an aggressive and highly lethal disease, which warrants the critical need to identify new therapeutic targets. We show that Zinc Fingers And Homeoboxes 2 (ZHX2) is amplified or overexpressed in TNBC cell lines and patients. Functionally, depletion of ZHX2 inhibited TNBC cell growth and invasion in vitro, orthotopic tumor growth and spontaneous lung metastasis in vivo. Mechanistically, ZHX2 bound with hypoxia inducible factor (HIF) family members and positively regulated HIF1 activity in TNBC. Integrated ChIP-Seq and gene expression profiling demonstrated that ZHX2 co-occupied with HIF1 on transcriptionally active promoters marked by H3K4me3 and H3K27ac, thereby promoting gene expression. Furthermore, multiple residues (R491, R581 and R674) on ZHX2 are important in regulating its phenotype, which correspond with their roles on controlling HIF1 activity in TNBC cells. These studies establish that ZHX2 activates oncogenic HIF1 signaling, therefore serving as a potential therapeutic target for TNBC.

cancer biology↗