Scinderin promotes the invasion and metastasis of gastric cancer cells and predicts the outcome of patients

Li, Jiajia; Liu, Junyan; Chen, Jun; Wu, Yalan; Peng, Yan; Ji, Chao; Wang, Yanxia; Xiang, Dongfang; Zhang, Xia; Zhang, Peng; Cui, You‐Hong; Wang, Ji Ming; Bian, Xiu‐Wu; Qian, Feng

doi:10.1016/j.canlet.2016.03.035

Cited by 42 publications

(46 citation statements)

References 41 publications

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“…A wound-healing assay was performed to examine the capability of cancer cell migration, as previously described 40 . Briefly, GC cells were grown in 24-well plates with RPMI-1640 medium supplemented with 10% FBS up to 90% confluence.…”

Section: Methodsmentioning

confidence: 99%

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FPR2 promotes invasion and metastasis of gastric cancer cells and predicts the prognosis of patients

Hou¹,

Ji²,

Tang³

et al. 2017

Sci Rep

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Formyl peptide receptor 2 (FPR2), a classical chemoattractant receptor of G-protein-coupled receptors, is reported to be involved in invasion and metastasis of some cancers, but the role of FPR2 in gastric cancer (GC) has not yet been elucidated. In this study, we found that the levels of FPR2 expression in GC were positively correlated with invasion depth, lymph node metastasis and negatively correlated with the patients’ overall survival. Multivariate analysis indicated that FPR2 expression was an independent prognostic marker for GC patients. FPR2-knockdown significantly abrogated the migration and invasion stimulated by Hp(2–20) and Ac(2–26), two well-characterized ligands for FPR2 in GC cells. FPR2 deletion also reduced the tumorigenic and metastatic capabilities of GC cells in vivo. Mechanistically, stimulation with FPR2 ligands resulted in down-regulation of E-cadherin and up-regulation of vimentin, which were reversed by FPR2 knock-down, implying the involvement of epithelial–mesenchymal transition (EMT). Moreover, the activation of FPR2 was accompanied with ERK1/2 phosphorylation, which could be attenuated by FPR2 silencing or treatment with MEK inhibitor, PD98059. Altogether, our results demonstrate that FPR2 is functionally involved in invasion and metastasis, and potentially acts as a novel prognostic marker as well as a potential therapeutic target in human GC.

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Section: Methodsmentioning

confidence: 99%

“…Invasion assay was performed as previously described 40 . Briefly, GC cells were seeded in the upper chamber (8 μm, 24-well format) coated with 10 μL of matrigel (BD, USA)/RPMI-1640 (1:1, v/v) at 2 × 104 cells/well in 200 μL RPMI-1640 medium without FBS.…”

Section: Methodsmentioning

confidence: 99%

FPR2 promotes invasion and metastasis of gastric cancer cells and predicts the prognosis of patients

Hou¹,

Ji²,

Tang³

et al. 2017

Sci Rep

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“…Lee et al 21 found that CAPZA1 is a marker for a good prognosis in GC and is associated with the decreased migration and invasion of cancer cells. Liu et al 47 reported that Scinderin inhibited the formation of filopodia and decreased the expression of CDC42 along with GC cell migration. Srivatsan et al 48 further indicated that knockdown of CD2AP in plasma cell‐like dendritic cells resulted in migration defects, and Zhao et al 49 found that CD2AP functions synergistically to enhance the function of cortactin, which enhances branched actin filament formation and promotes cell spreading and migration in mice podocytes.…”

Section: Discussionmentioning

confidence: 99%

CD2AP inhibits metastasis in gastric cancer by promoting cellular adhesion and cytoskeleton assembly

Xie

Chen

Zheng

et al. 2020

Molecular Carcinogenesis

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Diffuse gastric cancer (DGC) is a lethal malignancy lacking effective systemic therapy. Among the most provocative recent results in DGC has been that the alter of the cellular cytoskeleton and intercellular adhesion. CD2‐associated protein (CD2AP) is one of the critical proteins regulating cytoskeleton assembly and intercellular adhesion. However, no study has investigated the expression and biological significance of CD2AP in gastric cancer (GC) to date. Therefore, the aim of our study was to explore if the expression of CD2AP is associated with any clinical features of GC and to elucidate the underlying mechanism. Immunohistochemistry of 620 patient tissue samples indicated that the expression of CD2AP is downregulated in DGC. Moreover, a low CD2AP level was indicative of poor patient prognosis. In vitro, forced expression of CD2AP caused a significant decrease in the migration and invasion of GC cells, whereas depletion of CD2AP had the opposite effect. Immunofluorescence analysis indicated that CD2AP promoted cellular adhesion and influenced cell cytoskeleton assembly via interaction with the F‐actin capping protein CAPZA1. Overall, the upregulation of CD2AP could attenuate GC metastasis, suggesting CD2AP as a novel biomarker for the prognosis and treatment of patients with GC.

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“…Matrigel transwell analyses were performed as previously described (13 agonist and antagonist and signaling inhibitors on the invasiveness of GC cells, the metrigel-transwell system were cultured with or without ML133 (20 µM, TOCRIS) or Zacopride (10 µM, Sigma-Aldrich) or PD98059 (10 µM, Selleck) or LY3009120 (20 µM, Selleck). After incubation for 24 h at 37°C, the invasive cells were stained with 1% crystal violet and then counted from five random visual areas under a microscope.…”

Section: In Vitro Gc Cell Invasion Assaymentioning

confidence: 99%

“…Immunoblot analyses were performed as previously described (13). GC cells were washed twice with ice-cold PBS then lysed with protein extraction reagent (Thermo, USA) containing 1% protease inhibitors (Thermo, USA).…”

Section: Western Blotmentioning

confidence: 99%

Kir2.1 Interaction with Stk38 Promotes Invasion and Metastasis of Human Gastric Cancer by Enhancing MEKK2–MEK1/2–ERK1/2 Signaling

Wang

Xiang

et al. 2018

Cancer Research

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2 potassium channels; Kir2.1: inwardly rectifying potassium channel 2.1; Kv:voltage-gated channels; MEKK2: mitogen-activated protein kinase kinase kinase 2; OS: overall survival; PFS: progression-free survival; SDS-PAGE:SDS-polyacrylamide gel electrophoresis; Smurf1: small mothers against decapentaplegic-specific E3 ubiquitin protein ligase 1; Stk38:serine/threonine-protein kinase 38; TNBC: triple-negative breast cancer。 AbstractPotassium ion channels are emerging as pro-malignant factors involved in cancer progression. In this study, we found that invading human gastric cancer (GC) cells express high level of inwardly rectifying potassium channel 2.1 (Kir2.1). Silencing Kir2.1 markedly reduced the invasive and metastatic capabilities as well as the epithelial-mesenchymal transition (EMT) of GC cells. The pro-malignant nature of Kir2.1 in GC cells was independent of potassium permeation but relied on its interaction with serine/threonine-protein kinase 38 (Stk38) to inhibit ubiquitination and degradation of mitogen-activated protein kinase kinase kinase 2 (MEKK2).Degradation of MEKK2 was mediated by small mothers against decapentaplegic-specific E3 ubiquitin protein ligase 1 (Smurf1), which resulted in activation of the MEK1/2-ERK1/2-Snail pathway in GC cells. In human GC tissues, expression was high and positively correlated with invasion depth and metastatic status of the tumors as well as poor overall patient survival. Cox regression analysis identified Kir2.1 as an independent prognostic indicator for GC patients. Our results suggest that Kir2.1 is an important regulator of GC malignancy and acts as a novel prognostic marker and a therapeutic target for GC.

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Scinderin promotes the invasion and metastasis of gastric cancer cells and predicts the outcome of patients

Cited by 42 publications

References 41 publications

FPR2 promotes invasion and metastasis of gastric cancer cells and predicts the prognosis of patients

FPR2 promotes invasion and metastasis of gastric cancer cells and predicts the prognosis of patients

CD2AP inhibits metastasis in gastric cancer by promoting cellular adhesion and cytoskeleton assembly

Kir2.1 Interaction with Stk38 Promotes Invasion and Metastasis of Human Gastric Cancer by Enhancing MEKK2–MEK1/2–ERK1/2 Signaling

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