The Role of MAPK-ERK Pathway in 67-kDa Laminin Receptor-Induced FasL Expression in Human Cholangiocarcinoma Cells

Duan, Shengwen; Cheng, Long; Li, Dajiang; Zhu, Jun; Xiong, Yan; Li, Xiaowu; Wang, Shuguang

doi:10.1007/s10620-009-1121-9

Cited by 18 publications

(10 citation statements)

References 40 publications

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“…In order to analyse the molecular signalling connected to inhibitor treatment, and starting from previous observation of ERK1/2 pathway activation in AD patients with mild to severe pathology, together with previous reports showing 37/67 kDa LR-dependent regulation of MAPK phosphatases activity, which controls ERK signalling [52], we analysed pERK levels in inhibitor-treated GT1 cells compared to untreated control cells. Inactivation of ERK1/2 pathway in NSC48478 treated-cells was accompanied by increased Akt phosphorylation and consequent phospho-Ser9-GSK3β production ( Figure 11).…”

Section: Discussionmentioning

confidence: 99%

APP Maturation and Intracellular Localization Are Controlled by a Specific Inhibitor of 37/67 kDa Laminin-1 Receptor in Neuronal Cells

Bhattacharya

Limone

Napolitano

et al. 2020

IJMS

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Amyloid precursor protein (APP) is processed along both the nonamyloidogenic pathway preventing amyloid beta peptide (Aβ) production and the amyloidogenic pathway, generating Aβ, whose accumulation characterizes Alzheimer's disease. Items of evidence report that the intracellular trafficking plays a key role in the generation of Aβ and that the 37/67 kDa LR (laminin receptor), acting as a receptor for Aβ, may mediate Aβ-pathogenicity. Moreover, findings indicating interaction between the receptor and the key enzymes involved in the amyloidogenic pathway suggest a strong link between 37/67 kDa LR and APP processing. We show herein that the specific 37/67 kDa LR inhibitor, NSC48478, is able to reversibly affect the maturation of APP in a pH-dependent manner, resulting in the partial accumulation of the immature APP isoforms (unglycosylated/acetylated forms) in the endoplasmic reticulum (ER) and in transferrin-positive recycling endosomes, indicating alteration of the APP intracellular trafficking. These effects reveal NSC48478 inhibitor as a novel small molecule to be tested in disease conditions, mediated by the 37/67 kDa LR and accompanied by inactivation of ERK1/2 (extracellular signal-regulated kinases) signalling and activation of Akt (serine/threonine protein kinase) with consequent inhibition of GSK3β.

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Section: Discussionmentioning

confidence: 99%

APP Maturation and Intracellular Localization Are Controlled by a Specific Inhibitor of 37/67 kDa Laminin-1 Receptor in Neuronal Cells

Bhattacharya

Limone

Napolitano

et al. 2020

IJMS

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“…An increase in 67LR expression has been found in a variety of cancers including CCA [23, 24]. 67LR promotes CCA cell invasion and metastasis through various mechanisms, including facilitating tumour cell invasion into adjacent tissue by upregulating proteolytic enzymes [25, 26] and assisting tumour cell survival in the circulatory system by promoting immune privilege [27]. By targeting GATA6, miR-124 may also downregulate 67LR expression and play important roles in these processes during CCA cell metastasis.…”

Section: Discussionmentioning

confidence: 99%

miR-124 targets GATA6 to suppress cholangiocarcinoma cell invasion and metastasis

et al. 2017

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BackgroundOur previous study showed that GATA6 plays important roles in cholangiocarcinoma (CCA) cell invasion and metastasis. However, the regulation mechanism of GATA6 in CCA is not clear. In this study, we studied the potential function of miR-124 in CCA and the mechanism of GATA6 regulation.MethodsThe expression levels of miR-124 and GATA6 in cancerous tissues from 57 CCA patients was detected by RT-PCR and IHC. The impact of miR-124 on GATA6 expression in CCA cells was evaluated using cell transfection, xenotransplantation into nude mice and a luciferase reporter assay.ResultsmiR-124 was decreased in 57 cancerous tissue samples compared with 38 matched paracancerous samples. The miR-124 level was inversely associated with lymph node involvement and distant metastasis. miR-124 significantly inhibited invasion and migration of CCA cells in vitro. Furthermore, miR-124 inhibited CCA cell metastasis in nude mice. miR-124 inhibited the luciferase activity of reporter genes containing the wild-type GATA6 3′-UTR, which was abrogated by mutation of the binding site. The protein levels of GATA6 were negatively regulated by miR-124. miR-124 expression was inversely associated with GATA6 in 57 cancerous samples. The miR-124-induced suppression of CCA invasion was abrogated by remedial expression of GATA6. GATA6 expression was decreased by miR-124 overexpression in liver masses from nude mice.ConclusionsOur data suggested that miR-124 decreases GATA6 expression by targeting its 3′-UTR, which in turn inhibits CCA invasion and metastasis.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-017-3166-z) contains supplementary material, which is available to authorized users.

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“…Apoptosis via Fas/FasL system has been evidenced to play a role in the pathogenesis of many diseases [26][27][28][29][30][31][32][33][34].…”

Section: Discussionmentioning

confidence: 99%

Fas/Fas Ligand pathways gene polymorphisms in pediatric renal allograft rejection

Fadel

Elshamaa

Salah

et al. 2016

Transplant Immunology

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The Role of MAPK-ERK Pathway in 67-kDa Laminin Receptor-Induced FasL Expression in Human Cholangiocarcinoma Cells

Abstract: Based on these results, we conclude that 67LR induces FasL expression and cytotoxicity against Fas-sensitive Jurkat T cells in human cholangiocarcinoma cells through the phosphorylation of c-Myc on Ser-62 and the subsequent activation of the FasL promoter through the ERK pathway.

Cited by 18 publications

References 40 publications

APP Maturation and Intracellular Localization Are Controlled by a Specific Inhibitor of 37/67 kDa Laminin-1 Receptor in Neuronal Cells

APP Maturation and Intracellular Localization Are Controlled by a Specific Inhibitor of 37/67 kDa Laminin-1 Receptor in Neuronal Cells

miR-124 targets GATA6 to suppress cholangiocarcinoma cell invasion and metastasis

Fas/Fas Ligand pathways gene polymorphisms in pediatric renal allograft rejection

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