All Publications

  • Cell Extrusion: A Stress-Responsive Force for Good or Evil in Epithelial Homeostasis. Developmental cell Ohsawa, S. n., Vaughen, J. n., Igaki, T. n. 2018; 44 (3): 284–96


    Epithelial tissues robustly respond to internal and external stressors via dynamic cellular rearrangements. Cell extrusion acts as a key regulator of epithelial homeostasis by removing apoptotic cells, orchestrating morphogenesis, and mediating competitive cellular battles during tumorigenesis. Here, we delineate the diverse functions of cell extrusion during development and disease. We emphasize the expanding role for apoptotic cell extrusion in exerting morphogenetic forces, as well as the strong intersection of cell extrusion with cell competition, a homeostatic mechanism that eliminates aberrant or unfit cells. While cell competition and extrusion can exert potent, tumor-suppressive effects, dysregulation of either critical homeostatic program can fuel cancer progression.

    View details for DOI 10.1016/j.devcel.2018.01.009

    View details for PubMedID 29408235

  • Breaking Down Neighbors to Fuel Tumorigenesis. Developmental cell Vaughen, J., Igaki, T. 2017; 40 (3): 219-220


    Autophagy supports cell growth and survival autonomously by recycling intracellular proteins and/or organelles. Reporting in Nature, Katheder and colleagues (2017) find that tumors trigger non-autonomous autophagy in neighboring cells and distant organs, thus fueling tumor growth and metastasis. This opens new avenues for understanding and manipulating cancers through cell-cell communication.

    View details for DOI 10.1016/j.devcel.2017.01.011

    View details for PubMedID 28171745

  • Slit-Robo Repulsive Signaling Extrudes Tumorigenic Cells from Epithelia DEVELOPMENTAL CELL Vaughen, J., Igaki, T. 2016; 39 (6): 683-695


    Cells dynamically interact throughout animal development to coordinate growth and deter disease. For example, cell-cell competition weeds out aberrant cells to enforce homeostasis. In Drosophila, tumorigenic cells mutant for the cell polarity gene scribble (scrib) are actively eliminated from epithelia when surrounded by wild-type cells. While scrib cell elimination depends critically on JNK signaling, JNK-dependent cell death cannot sufficiently explain scrib cell extirpation. Thus, how JNK executed cell elimination remained elusive. Here, we show that repulsive Slit-Robo2-Ena signaling exerts an extrusive force downstream of JNK to eliminate scrib cells from epithelia by disrupting E-cadherin. While loss of Slit-Robo2-Ena in scrib cells potentiates scrib tumor formation within the epithelium, Robo2-Ena hyperactivation surprisingly triggers luminal scrib tumor growth following excess extrusion. This extrusive signaling is amplified by a positive feedback loop between Slit-Robo2-Ena and JNK. Our observations provide a potential causal mechanism for Slit-Robo dysregulation in numerous human cancers.

    View details for DOI 10.1016/j.devcel.2016.11.015

    View details for Web of Science ID 000390576200009

    View details for PubMedID 27997825

  • Non-autonomous overgrowth by oncogenic niche cells: Cellular cooperation and competition in tumorigenesis CANCER SCIENCE Enomoto, M., Vaughen, J., Igaki, T. 2015; 106 (12): 1651-1658


    Tumor progression is classically viewed as the Darwinian evolution of subclones that sequentially acquire genetic mutations and autonomously overproliferate. However, growing evidence suggests that tumor microenvironment and subclone heterogeneity contribute to non-autonomous tumor progression. Recent Drosophila studies revealed a common mechanism by which clones of genetically altered cells trigger non-autonomous overgrowth. Such "oncogenic niche cells" (ONCs) do not overgrow but instead stimulate neighbor overgrowth and metastasis. Establishment of ONCs depends on competition and cooperation between heterogeneous cell populations. This review characterizes diverse ONCs identified in Drosophila and describes the genetic basis of non-autonomous tumor progression. Similar mechanisms may contribute to mammalian cancer progression and recurrence.

    View details for DOI 10.1111/cas.12816

    View details for Web of Science ID 000368249400001

    View details for PubMedID 26362609

    View details for PubMedCentralID PMC4714670