Biology subjects

Kwon, Y. V.

Publications and source records attributed to Kwon, Y. V..

4 recordsLinked to original sources

bioRxiv2022

The native cell differentiation program aberrantly recapitulated in yki3S/A-induced intestinal hyperplasia drives invasiveness and cachexia-like wasting phenotypes

Many tumors recapitulate the developmental and differentiation program of their tissue of origin, a basis for tumor cell heterogeneity. Although stem-cell-like tumor cells are well-studied, the roles of tumor cells undergoing differentiation in inducing the phenotypes associated with advanced cancers remains to be elucidated. Here, we employ Drosophila genetics to demonstrate that the native differentiation program of intestinal stem cells plays a key role in determining an intestinal tumors capacity to invade and induce various non-tumor-autonomous phenotypes. The differentiation program that generates absorptive cells enterocytes is aberrantly recapitulated in the intestinal tumors generated through activation of the Yap1 ortholog Yorkie. Elimination of tumor cells in the enterocyte lineage allows stem cell-like tumor cells to grow but suppresses invasiveness and reshapes various phenotypes associated with cachexia-like wasting by altering the expression of tumor-derived factors. Our study provides insight into how a native differentiation program determines a tumors capacity to induce the phenotypes associated with advanced cancers and suggests that manipulating the differentiation programs co-opted in tumors might be a way to treat some complications of cancer, including cachexia.

developmental biology↗

bioRxiv2021

The roles of distinct Ca2+ signaling mediated by Piezo and inositol triphosphate receptor (IP3R) in the remodeling of E-cadherin during cell dissemination

Given the role of E-cadherin (E-cad) in holding epithelial cells together, the inverse relationship between E-cad levels and cell invasion has been perceived as a principle underlying the invasiveness of tumor cells. In contrast, our study employing the Drosophila model of cell dissemination demonstrates that E-cad is necessary for the invasiveness of Rasv12-transformed cells in vivo. Drosophila E-cad/{beta}-catenin disassembles at adherens junctions and assembles at invasive protrusions--the actin- and cortactin-rich invadopodia-like protrusions associated with breach of the extracellular matrix (ECM)--during cell dissemination. Loss of E-cad attenuates dissemination of Rasv12-transformed cells by impairing their ability to compromise the ECM. Strikingly, the remodeling of E-cad/{beta}-catenin subcellular distribution is controlled by two discrete intracellular calcium signaling pathways: Ca2+ release from endoplasmic reticulum via the inositol triphosphate receptor (IP3R) disassembles E-cad at adherens junctions while Ca2+ entry via the mechanosensitive channel Piezo assembles E-cad at invasive protrusions. Thus, our study provides molecular insights into the unconventional role of E-cad in cell invasion during cell dissemination in vivo and describes the discrete roles of intracellular calcium signaling in the remodeling of E-cad/{beta}-catenin subcellular localization.

cell biology↗

bioRxiv2021

Wear and Tear of the Intestinal Visceral Musculature by Intrinsic and Extrinsic Factors

The gut visceral musculature plays essential roles in not only moving substances through the lumen but also maintaining the function and physiology of the gut. Although the development of the visceral musculature has been studied in multiple model organisms, how it degenerates is poorly understood. Here, we employ the Drosophila midgut as a model to demonstrate that the visceral musculature is disrupted by intrinsic and extrinsic factors, such as aging, feeding, chemical-induced tissue damage, and oncogenic transformation in the epithelium. Notably, we define four prominent visceral musculature disruption phenotypes, which we refer as sprout, discontinuity, furcation, and crossover of the longitudinal muscle. Given that the occurrence of these phenotypes is increased during aging and under various stresses, we propose that these phenotypes can be used as quantitative readouts of deterioration of the visceral musculature. Intriguingly, administration of a tissue-damaging chemical dextran sulfate sodium (DSS) induced similar visceral musculature disruption phenotypes in zebrafish larvae, indicating that ingestion of a tissue-damaging chemical can disrupt the visceral musculature in a vertebrate as well. Our study provides insights into the deterioration of the gut visceral musculature and lays a groundwork for investigating the underlying mechanisms in Drosophila as well as other animals.

developmental biology↗

bioRxiv2020

Tumors Negate the Action of ImpL2 by Elevating Wingless

Tumors often secrete wasting factors associated with atrophy and degeneration of host tissues. If tumors were affected by the wasting factors, mechanisms allowing tumors to evade the adverse effects of the wasting factors must exist and impairing such mechanisms may attenuate tumors. We used Drosophila midgut tumor models to show that tumors upregulate Wingless (Wg) to oppose the growth-impeding effects caused by the wasting factor, ImpL2 (Insulin-like growth factor binding protein (IGFBP)-related protein). Growth of Yorkie (Yki)-induced tumors is dependent on Wg while either elimination of ImpL2 or elevation of Insulin/IGF signaling in tumors revokes this dependency. Notably, Wg augmentation could be a general mechanism for supporting the growth of tumors with elevated ImpL2 and exploited to attenuate muscle degeneration during wasting. Our study elucidates the mechanism by which tumors negate the action of ImpL2 and implies that targeting the Wnt/Wg pathway might be an efficient treatment strategy for cancers with elevated IGFBPs.

cancer biology↗