Downregulation of tight junction-associated MARVEL protein marvelD3 during epithelial–mesenchymal transition in human pancreatic cancer cells

Kojima, Takashi; Takasawa, Akira; Kyuno, Daisuke; Itô, Tatsuya; Yamaguchi, Hiroshi; Hirata, Koichi; Tsujiwaki, Mitsuhiro; Murata, Masaki; Tanaka, Satoshi; Sawada, Norimasa

doi:10.1016/j.yexcr.2011.06.020

Cited by 49 publications

(57 citation statements)

References 32 publications

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“…In a trend similar to that seen with tricellulin in gastric cancer (80), MarvelD3 has been described as highly expressed in well-differentiated pancreatic cancer cells but less well expressed in poorly-differentiated pancreatic cancer cells co-expressing the transcription factor snail (76). Accordingly the induction of EMT by snail downregulated MarvelD3 in highly differentiated pancreatic cancer cells (76), and, in a …”

Section: Marveld3supporting

confidence: 58%

“…Expression of MarvelD3 has been noted in endothelial cells of the brain, cornea, umbilical vein and in murine/human epithelial cells of the cornea, prostate, small intestine, colon, stomach, liver, kidney, spleen and pancreas (73,76,82). Gene silencing experiments have revealed that MarvelD3 is not required for epithelial tight junction formation, but that it may influence paracellular permeability of established epithelial barriers (82).…”

Section: Marveld3mentioning

confidence: 99%

“…Specifically, its expression has been observed in colon, pancreatic, lung, colorectal and breast cancer tissues (73,76,82,84,85), with mounting evidence pointing towards its regulatory functions more than its structural role. In a trend similar to that seen with tricellulin in gastric cancer (80), MarvelD3 has been described as highly expressed in well-differentiated pancreatic cancer cells but less well expressed in poorly-differentiated pancreatic cancer cells co-expressing the transcription factor snail (76).…”

Section: Marveld3mentioning

confidence: 99%

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The Contribution of Ig-Superfamily and MARVEL D Tight Junction Proteins to Cancer Pathobiology

et al. 2016

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Word count (abstract-conclusion inclusive) = 4,1252 AbstractThe epithelial linings of eukaryotic organs form dynamically-regulated selectively-permeable barriers that control the movement of substances into (and out of) mucosal tissues. The principal structural determinants of epithelial barrier function are intercellular tight junctions (TJs), multi-protein complexes composed of claudin and non-claudin transmembrane proteins in addition to cytosolic linker proteins. As well as their crucial roles in barrier function, it is now well recognized that TJ proteins coordinate a variety of signaling and trafficking functions regulating physiological events such as cell differentiation, proliferation, migration and polarity. Accordingly, dysregulations in TJ protein expression or function are increasingly being linked to several pathophysiologies including cancer. To date, claudins have received the most attention as putative contributors to cancer initiation or progression.However the contribution of non-claudin transmembrane TJ proteins (including select immunoglobulin superfamily members, nectins, occludin and Marvel D family members) to the pathophysiology of cancer remains incompletely understood. Therefore the focus of this review is to collate recently-published evidence that supports or discounts a role for nonclaudin transmembrane TJ proteins in cancer, and to speculate upon the feasibility of these molecules as prognostic biomarkers or therapeutic targets in cancer.3

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Section: Marveld3supporting

confidence: 58%

Section: Marveld3mentioning

confidence: 99%

Section: Marveld3mentioning

confidence: 99%

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The Contribution of Ig-Superfamily and MARVEL D Tight Junction Proteins to Cancer Pathobiology

et al. 2016

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“…In cultured metastatic tumour cell lines, MarvelD3 expression is repressed, suggesting that it also regulates cell behaviour (Kojima et al, 2011;Steed et al, 2014). Manipulation of MarvelD3 expression indeed affects epithelial cell proliferation and migration through a mechanism that involves the recruitment of MEKK1 (also known as mitogenactivated protein kinase kinase kinase 1, MAP3K1) to tight junctions, leading to inhibition of the c-jun N-terminal kinase (JNK) pathway and downregulation of genes that regulate proliferation, such as cyclin D1 (Steed et al, 2014).…”

Section: Regulation Of Cell Behaviour and Survival By Transmembrane Pmentioning

confidence: 99%

Signalling at tight junctions during epithelial differentiation and microbial pathogenesis

Zihni

Balda

Matter

2014

Journal of Cell Science

106

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Tight junctions are a component of the epithelial junctional complex, and they form the paracellular diffusion barrier that enables epithelial cells to create cellular sheets that separate compartments with different compositions. The assembly and function of tight junctions are intimately linked to the actomyosin cytoskeleton and, hence, are under the control of signalling mechanisms that regulate cytoskeletal dynamics. Tight junctions not only receive signals that guide their assembly and function, but transmit information to the cell interior to regulate cell proliferation, migration and survival. As a crucial component of the epithelial barrier, they are often targeted by pathogenic viruses and bacteria, aiding infection and the development of disease. In this Commentary, we review recent progress in the understanding of the molecular signalling mechanisms that drive junction assembly and function, and the signalling processes by which tight junctions regulate cell behaviour and survival. We also discuss the way in which junctional components are exploited by pathogenic viruses and bacteria, and how this might affect junctional signalling mechanisms.

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“…To investigate changes of claudin-1, -4, -7 and occludin following PKC activation in the human pancreatic cancer cell line HPAC, in which tight junction molecules claudin-1, -4, -7, occludin, tricellulin and marvelD3 were previously detected Kojima et al 2010Kojima et al , 2011, the cells were treated with 1-100 nM TPA for 24 h. In Western blots, claudin-1 and E-cadherin were decreased and Snail was increased from 10 nM TPA in HPAC cells, whereas no change of claudin-4, -7 and occludin was observed (Fig. 1a).…”

Section: Downregulation Of Claudin-1 By Pkc Activation In Hpac Cellsmentioning

confidence: 99%

Protein kinase Cα inhibitor enhances the sensitivity of human pancreatic cancer HPAC cells to Clostridium perfringens enterotoxin via claudin-4

et al. 2011

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Protein kinase C (PKC) is overexpressed in cancer, including pancreatic cancer, compared with normal tissue. Moreover, PKCα is considered one of the biomarkers for the diagnosis of cancers. In several human cancers, the claudin tight junction molecules are abnormally regulated and are thus promising molecular targets for diagnosis and therapy with Clostridium perfringens enterotoxin (CPE). In order to investigate the changes of tight junction functions of claudins via PKCα activation in pancreatic cancer cells, the well-differentiated human pancreatic cancer cell line HPAC, with its highly expressed tight junction molecules and well-developed barrier function, was treated with the PKC activator 12-O-tetradecanoylphorbol 13-acetate (TPA). Treatment with TPA modified the activity of phosphoPKCα and caused an increase of the Snail family members Snail, Slug and Smad-interacting protein 1 and a decrease of E-cadherin. In HPAC cells treated with TPA, downregulation of claudin-1 and mislocalization of claudin-4 and occludin around the nuclei were observed, together with a decrease in the numbers of tight junction strands and an increase in phosphorylation of claudin-4. The barrier function and the cytotoxicity of CPE were significantly decreased on TPA treatment. All such changes after TPA treatment were prevented by inhibitors of panPKC and PKCα. These findings suggest that, in human pancreatic cancer cells, PKCα activation downregulates tight junction functions as a barrier and as a receptor of CPE via the modification of claudin-1 and -4 during epithelial to mesenchymal transition-like changes. PKCα inhibitors might represent potential therapeutic agents against human pancreatic cancer cells by use of CPE cytotoxicity via claudin-4.

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Downregulation of tight junction-associated MARVEL protein marvelD3 during epithelial–mesenchymal transition in human pancreatic cancer cells

Cited by 49 publications

References 32 publications

The Contribution of Ig-Superfamily and MARVEL D Tight Junction Proteins to Cancer Pathobiology

The Contribution of Ig-Superfamily and MARVEL D Tight Junction Proteins to Cancer Pathobiology

Signalling at tight junctions during epithelial differentiation and microbial pathogenesis

Protein kinase Cα inhibitor enhances the sensitivity of human pancreatic cancer HPAC cells to Clostridium perfringens enterotoxin via claudin-4

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