Zonula occludens-2 regulates Rho proteins activity and the development of epithelial cytoarchitecture and barrier function

Raya‐Sandino, Arturo; Castillo‐Kauil, Alejandro; Domínguez-Calderón, Alaide; Alarcón, Lourdes; Flores-Benítez, David; Cuellar-Perez, Francisco; López-Bayghen, Bruno; Chávez‐Munguía, Bibiana; Vázquez‐Prado, José; González‐Mariscal, Lorenza

doi:10.1016/j.bbamcr.2017.05.016

Cited by 40 publications

(61 citation statements)

References 96 publications

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“…A stable MDCK cell line was created which expressed E7, and it was found that the monolayers had widened intercellular spaces and had areas in which some cells were growing on top of one another. A similar phenotype was observed in MDCK monolayers where the expression of the TJ protein ZO-2 was knocked down (161,162), which suggests that the E7 oncoprotein exerts a harmful effect on TJs. However, when the development of TER in MDCK-E7 monolayers was analyzed it was found that they achieved a higher peak of TER compared with that in parental cells.…”

Section: Discussionsupporting

confidence: 62%

E7 oncoprotein from human papillomavirus 16 alters claudins expression and the sealing of epithelial tight junctions

Uc¹,

Miranda²,

Raya‐Sandino³

et al. 2020

Int J Oncol

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Tight junctions (TJs) are cell-cell adhesion structures frequently altered by oncogenic transformation. In the present study the role of human papillomavirus (HPV) 16 E7 oncoprotein on the sealing of TJs was investigated and also the expression level of claudins in mouse cervix and in epithelial Madin-Darby Canine Kidney (MDCK) cells. It was found that there was reduced expression of claudins-1 and-10 in the cervix of 7-month-old transgenic K14E7 mice treated with 17β-estradiol (E 2), with invasive cancer. In addition, there was also a transient increase in claudin-1 expression in the cervix of 2-month-old K14E7 mice, and claudin-10 accumulated at the border of cells in the upper layer of the cervix in FvB mice treated with E 2 , and in K14E7 mice treated with or without E 2. These changes were accompanied by an augmented paracellular permeability of the cervix in 2-and 7-month-old FvB mice treated with E 2 , which became more pronounced in K14E7 mice treated with or without E 2. In MDCK cells the stable expression of E7 increased the space between adjacent cells and altered the architecture of the monolayers, induced the development of an acute peak of transepithelial electrical resistance accompanied by a reduced expression of claudins-1,-2 and-10, and an increase in claudin-4. Moreover, E7 enhances the ability of MDCK cells to migrate through a 3D matrix and induces cell stiffening and stress fiber formation. These observations revealed that cell transformation induced by HPV16 E7 oncoprotein was accompanied by changes in the pattern of expression of claudins and the degree of sealing of epithelial TJs.

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Section: Discussionsupporting

confidence: 62%

E7 oncoprotein from human papillomavirus 16 alters claudins expression and the sealing of epithelial tight junctions

Uc¹,

Miranda²,

Raya‐Sandino³

et al. 2020

Int J Oncol

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“…CIC‐TEX‐promoted cld7kd cell dissemination in vivo and tumor cell motility and invasiveness in vitro are particularly interesting as palmitoylated cld7 is located in tetraspanin‐associated LN‐binding integrins‐ and proteases‐containing GEM and TJ‐located cld7 is associated with Zo‐1 and cingulin, which regulates TJ gene expression and JUP, a hub gene in CoCa . In vivo , the CIC‐TEX‐promoted rescue of impaired cld7kd cell migration was accompanied by Tspan8, CD104 and slightly CD49c upregulation by CIC‐TEX‐, but not cld7mP‐TEX‐treatment, indicating GEM‐derived CIC‐TEX cooperating with tetraspanin‐associated integrins .…”

Section: Discussionmentioning

confidence: 99%

Claudin7‐dependent exosome‐promoted reprogramming of nonmetastasizing tumor cells

Kyuno

Zhao

Schnölzer

et al. 2019

Intl Journal of Cancer

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Claudin7 (cld7) is a cancer‐initiating cell (CIC) marker in gastrointestinal tumors, a cld7‐knockdown (kd) being accompanied by loss of tumor progression. Tumor exosomes (TEX) restoring CIC activities, we explored the contribution of cld7. This became particularly interesting, as tight junction (TJ)‐ and glycolipid‐enriched membrane domain (GEM)‐derived cld7 is recruited into distinct TEX. TEXs were derived from CIC or cld7kd cells of a rat pancreatic and a human colon cancer line. TEX derived from pancreatic cancer cld7kd cells rescued with palmitoylation site‐deficient cld7 (cld7mP) allowed selectively evaluating the contribution of GEM‐derived TEX, only palmitoylated cld7 being integrated into GEM. Cld7 CIC‐TEX promoted tumor cell dissemination and metastatic growth without a major impact on proliferation, apoptosis resistance and epithelial–mesenchymal transition. Instead, migration, invasion and (lymph)angiogenesis were strongly supported, only migration being selectively fostered by GEM‐derived cld7 TEX. CIC‐TEX coculture of cld7kd cells uncovered significant changes in the cld7kd cell protein and miRNA profiles. However, changes did not correspond to the CIC‐TEX profile, CIC‐TEX rather initiating integrin, protease and RTK, particularly lymphangiogenic receptor activation. CIC‐TEX preferentially rescuing cld7kd‐associated defects in signal transduction was backed up by an RTK inhibitor neutralizing the impact of CIC‐TEX on tumor progression. In conclusion, cld7 contributes to selective steps of the metastatic cascade. Defects of cld7kd and cld7mP cells in migration, invasion and (lymph)angiogenesis are effaced by CIC‐TEX that act by signaling cascade activation. Accordingly, RTK inhibitors are an efficient therapeutic defeating CIC‐TEX.

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“…Another TJ protein, ZO-2, was recently shown to have a role in promoting GEF-H1 inhibition through phosphorylation. 128…”

Section: Gef-h1mentioning

confidence: 99%

The role of microtubules in the regulation of epithelial junctions

Vasileva

Citi

2018

Tissue Barriers

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The cytoskeleton is crucially important for the assembly of cell-cell junctions and the homeostatic regulation of their functions. Junctional proteins act, in turn, as anchors for cytoskeletal filaments, and as regulators of cytoskeletal dynamics and signalling proteins. The cross-talk between junctions and the cytoskeleton is critical for the morphogenesis and physiology of epithelial and other tissues, but is not completely understood. Microtubules are implicated in the delivery of junctional proteins to cell-cell contact sites, in the differentiation and spatial organization of the cytoplasm, and in the stabilization of the barrier and adhesive functions of junctions. Here we focus on the relationships between microtubules and junctions of vertebrate epithelial cells. We highlight recent discoveries on the molecular underpinnings of microtubulejunction interactions, and report new data about the interaction of cingulin and paracingulin with microtubules. We also propose a possible new role of junctions as "molecular sinks" for microtubule-associated signalling proteins.

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Zonula occludens-2 regulates Rho proteins activity and the development of epithelial cytoarchitecture and barrier function

Cited by 40 publications

References 96 publications

E7 oncoprotein from human papillomavirus 16 alters claudins expression and the sealing of epithelial tight junctions

E7 oncoprotein from human papillomavirus 16 alters claudins expression and the sealing of epithelial tight junctions

Claudin7‐dependent exosome‐promoted reprogramming of nonmetastasizing tumor cells

The role of microtubules in the regulation of epithelial junctions

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