Assistant Professor Email: yany@ust.hk Division of Life Science, HKUST Office: Room 5455, Academic Building Tel: (852)2358-5929 Laboratory webpage: http://yanlab.ust.hk

My laboratory uses Drosophila and mammalian cells as cancer models to study the molecular and cellular mechanisms of growth control and metastasis.

1). Mechanism of cell competition induced by polarity-deficient cells.

Scribble (Scrib), Discs large (Dlg) and Lethal giant larvae (Lgl) belong to a group of “neoplastic tumor suppressor genes” (nTSGs) originally identified in Drosophila. When imaginal discs are homozygous mutant for one of the scribble group genes, the mutant cells fail to differentiate, lose proliferation control, and grow into invasive tumors. These mutant cells can survive serial transplantations to other host animals, continue to proliferate and kill the hosts. In human, deregulation of the Scribble complex is linked with tumor progression in multiple types of cancers.

Interestingly, when nTSG mutant cells are induced as mosaic clones and they are surrounded by wild-type cells, the mutant cells undergo JNK-dependent cell death through a cell competition process. The cell competition process is regarded as an intrinsic surveillance system to eliminate tumorigenic cells with polarity defects. How this process is regulated remains largely unclear.

Through transcriptome profiling and genetic screening, we have identified a number of previously unknown genes modulating the fate of nTSG mutant cells during the cell competition process. With these newly identified components and our established Drosophila and mammalian cell competition platforms, we are working towards a better understanding of the molecular network that regulates cell competition induced by polarity-deficient cells.

2). Molecular and cellular mechanism of single cell extrusion.

Single cell extrusion from the epithelium is a process important for generation of diverse cell types, organ formation and tissue homeostasis. Single cells extruded from a cell community can either undergo apoptosis or continue to proliferate and differentiate. It is largely unclear how the single cell extrusion process is regulated and how the life-or-death fate of extruded cells is regulated, a critical problem at the initial stage of tumor metastasis.

 We have developed Drosophila ventral nerve cord (VNC) neural stem cells (neuroblasts) as a model to study single cell extrusion from the epithelial layer. While in many other developmental contexts single cell extrusion events are difficult to track with limited optical accessibility, Drosophila VNC neuroblasts delaminate from the embryo surface at predictable times and places. Through quantitative imaging, genetic experiments and mathematical modeling, we are able to track and model the single cell extrusion process with exquisite spatiotemporal precision.

Representative Publications

1. Apical constriction is driven by a pulsatile apical myosin network in delaminating Drosophila neuroblasts, Yanru An, Guosheng Xue, Yang Shaobo, Deng Mingxi, Xiaowei Zhou, Weichuan Yu, Toyotaka Ishibashi, Lei Zhang, Yan Yan, Accepted in Development.
   
   
2. Wong KK, Li W, An Y, Duan Y, Li Z, Kang Y, Yan Y*. β-Spectrin regulates the Hippo signaling pathway and modulates the basal actin network. J Biol Chem, 2015, In press.
    
3. Li Y, Wei Z, Yan Y, Wan Q, Du Q, Zhang M. Structure of Crumbs tail in complex with the PALS1 PDZ-SH3-GK tandem reveals a highly specific assembly mechanism for the apical Crumbs complex. Proc Natl Acad Sci USA. 2014 Dec 9;111(49):17444-9.
    
4. Yan Y, Denef N, Tang C, Schupbach T, Drosophila PI4KIIIalpha is required in the follicle cells for oocyte polarization and Hippo signaling. Development. 2011 May;138(9):1697-703.
   • Highlighted in “Editors’ choice”: VanHook AM, Lipids Influence Hippo Signaling. Sci. Signal. 4, ec110 (2011)
    
5. Yan Y*, Denef N*, Schupbach T, The vacuolar proton pump, V-ATPase, is required for Notch signaling and endosomal trafficking in Drosophila. Dev Cell. 2009 Sep;17(3):387-402. *These authors contribute equally to this work.
   • Highlighted in Faculty of 1000 Biology: http://f1000.com/1166515
    
6. Sun Y, Yan Y, Denef N, Schupbach T, Regulation of Somatic Myosin Activity by Protein Phosphatase 1beta Controls Drosophila Oocyte Polarization. Development. 2011 May;138(10):1991-2001.
    
7. Sethi N, Yan Y, Quek D, Schupbach T, Kang Y, Rabconnectin-3 is a functional regulator of mammalian Notch signaling. J Biol Chem. 2010 Nov 5;285(45):34757-64.

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