Involvement of Dystroglycan in Epithelial-Mesenchymal Transition during Chick Gastrulation

Abstract

Regulated disruption of the basement membrane (BM) is a critical step in many epithelial-mesenchymal transition (EMT) processes. Molecular mechanisms controlling the interaction between the BM and the basal membrane of epithelial cells and its subsequent disruption during EMT are poorly understood. Using chick embryos as a model, we analyzed the molecular complexity of this interaction during gastrulation EMT. Transcriptome data indicated that the BM of the gastrulation stage chick epiblast contains a full range of BM component proteins with unique subtype combinations. Integrins and dystroglycan are 2 major groups of basal membrane proteins involved in BM interaction. We provide evidence that dystroglycan gene expression is restricted to the epiblast during early development and its expression is downregulated in cells undergoing gastrulation EMT. The β-dystroglycan protein is localized to the basolateral membrane in epiblast cells and the basal localization is lost in cells undergoing EMT. Disruption of actin filaments leads to a decrease in the lateral membrane localization of β-dystroglycan and a relative increase in basal membrane localization, whereas disruption of microtubules leads to the loss of BM/basal membrane interaction and basal membrane β-dystroglycan localization. Overall, these data suggest an involvement of dystroglycan, especially the regulation of its expression and localization, in gastrulation EMT.

DecreasedSMAD4expression is associated with induction of epithelial-to-mesenchymal transition and cetuximab resistance in head and neck squamous cell carcinoma

“…26,27 In carcinogenesis, the migratory phenotype and increased plasticity associated with EMT provides many advantages for a developing malignancy to evolve and evade traditional therapies leading to distant metastasis. Thus, it is important to elucidate the molecular determinants of EMT in a diseasespecific manner to improve therapeutic outcomes in HNSCC.…”

ROCK1-directed basement membrane positioning coordinates epithelial tissue polarity

“…PAR-1b regulates microtubule dynamics (Drewes et al, 1997) via its phosphorylation of microtubule-associated proteins (MAPs) and the acquisition of a polarized microtubule array (Cohen et al, 2004;Cox et al, 2001;Doerflinger et al, 2003). In chick epithelial cells, a polarized microtubule array is required to maintain basement membrane stability, possibly through the stabilization of basally localized basement membrane receptors (Nakaya et al, 2011;Nakaya et al, 2008). Alternatively, a polarized microtubule array may be required for the polarized secretion of basement membrane components (Gilbert et al, 1991;Grindstaff et al, 1998), which could also explain the generalized defect in basement membrane deposition observed upon PAR-1b siRNA knockdown in the salivary gland organ cultures.…”

Polarization and Myelination in Myelinating Glia

“…Dystroglycan may antagonize EMT through keeping epithelial cell polarity by providing extrinsic polarity cues. Actually, involvement of dystroglycan in EMT was suggested [298]. Whereas the mechanism of how loss of apico-basal polarity leads to carcinogenesis remains unknown, inhibition of AMPK leads to carcinogenesis.…”