Osteoblast-derived WISP-1 increases VCAM-1 expression and enhances prostate cancer metastasis by down-regulating miR-126

Tai, Huai‐Ching; Chang, An‐Chen; Yu, Hong-Jeng; Huang, Chao Yuan; Tsai, Yu‐Chieh; Lai, Yu-Wei; Sun, Hui-Lung; Tang, Chih-Hsin; Wang, Shih‐Wei

doi:10.18632/oncotarget.2280

Cited by 51 publications

(39 citation statements)

References 41 publications

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“…As with Wnt2, WISP-1 has been studied in cancer cells, where it has been shown to be a chemoattractant, 20 encourage metastasis, 29 increase invasiveness, and decrease chances of survival. [30][31][32] WISP-1 has also been shown in human cancer cells to be upregulated compared with healthy cells 33 and to stimulate migration via NFκB activation of MMP-2.…”

Section: Arterioscler Thromb Vasc Biolmentioning

confidence: 99%

Wnt2 and WISP-1/CCN4 Induce Intimal Thickening via Promotion of Smooth Muscle Cell Migration

Williams

Mill

Monk

et al. 2016

ATVB

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Objective-Increased vascular smooth muscle cell (VSMC) migration leads to intimal thickening which acts as a soil for atherosclersosis, as well as causing coronary artery restenosis after stenting and vein graft failure. Investigating factors involved in VSMC migration may enable us to reduce intimal thickening and improve patient outcomes. In this study, we determined whether Wnt proteins regulate VSMC migration and thereby intimal thickening. Approach and Results-Wnt2 mRNA and protein expression were specifically increased in migrating mouse aortic VSMCs.Moreover, VSMC migration was induced by recombinant Wnt2 in vitro. Addition of recombinant Wnt2 protein increased Wnt1-inducible signaling pathway protein-1 (WISP-1) mRNA by ≈1.7-fold, via β-catenin/T-cell factor signaling, whereas silencing RNA knockdown of Wnt-2 reduced WISP-1 mRNA by ≈65%. Treatment with rWISP-1 significantly increased VSMC migration by ≈1.5-fold, whereas WISP-1 silencing RNA knockdown reduced migration by ≈40%. was not translated into protein, and recombinant Wnt2 (rWnt2) protein did not increase VSMC proliferation in vitro. 5 The Wnt pathway has also been shown to have a role in cell migration, with Wnt3a involvement in both migration and adhesion of VSMCs through integrin linked kinase regulation of β1-integrin.10 However, on initiation of this study, it was unclear which Wnt proteins modulated VSMC growth factor-induced migration and whether Wntinduced VSMC migration promoted intimal thickening in vivo. Many genes are upregulated by the Wnt pathway, some of which are known to modulate VSMC migration, including Wnt-1-inducible signaling pathway protein-1 (WISP-1/CCN4 Materials and MethodsMaterials and Methods are available in the online-only Data supplement. Nonstandard Abbreviations and Acronyms Results Wnt2 Was Upregulated in Migrating VSMCs In VitroWnt mRNA levels during VSMC migration were assessed using an in vitro scratch wound assay with multiple wounds to stimulate migration of the VSMCs. mRNA was extracted from VSMCs and applied to a focussed Wnt pathway microarray to assess whether the level of expression changed during migration. A significant increase was only observed in Wnt2 mRNA ( Figure 1A), and this change was confirmed using quantitative polymerase chain reaction ( Figure 1A). No significant change was seen in the mRNA levels of any other Wnts (see Table III in the online-only Data Supplement). It was observed by Western blotting ( Figure 1B) and immunocytochemistry ( Figure I in the online-only Data Supplement) that the increase in Wnt2 mRNA was translated into augmented Wnt2 protein levels in migrating VSMCs. Migrating VSMCs on the wound edge could be seen to express higher levels of Wnt2 protein than nonmigratory VSMCs further away from the wound edge ( Figure I in the online-only Data Supplement). Wnt2 Promoted VSMC Migration In VitroAddition of rWnt2 protein significantly increased VSMC migration in vitro, whereas knockdown of Wnt2 using silencing RNA (siRNA) inhibited migration ( Figure 1C). When rWnt2 was ad...

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Section: Arterioscler Thromb Vasc Biolmentioning

confidence: 99%

Wnt2 and WISP-1/CCN4 Induce Intimal Thickening via Promotion of Smooth Muscle Cell Migration

Williams

Mill

Monk

et al. 2016

ATVB

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“…Cells were seeded on six-well plates, then transiently transfected with VEGF-C 3 -UTR luciferase plasmids using Lipofectamine 2000 as described previously [37]. Cells collected were lysed with reporter lysis buffer 24 h after transfection, and the luciferase and Renilla activities in the cellular extracts were determined by the dual-luciferase reporter assay kit.…”

Section: Luciferase Reporter Assaymentioning

confidence: 99%

Adiponectin promotes VEGF-C-dependent lymphangiogenesis by inhibiting miR-27b through a CaMKII/AMPK/p38 signaling pathway in human chondrosarcoma cells

et al. 2016

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Chondrosarcoma is the second most frequently occurring type of bone malignancy characterized by distant metastatic propensity. Vascular endothelial growth factor-C (VEGF-C) is the major lymphangiogenic factor, and makes crucial contributions to tumour lymphangiogenesis and lymphatic metastasis. Adiponectin is a protein hormone secreted predominantly by differentiated adipocytes. In recent years, adiponectin has also been indicated as facilitating tumorigenesis, angiogenesis and metastasis. However, the effect of adiponectin on VEGF-C regulation and lymphangiogenesis in chondrosarcoma has remained largely a mystery. In the present study, we have shown a clinical correlation between adiponectin and VEGF-C, as well as tumour stage, in human chondrosarcoma tissues. We further demonstrated that adiponectin promoted VEGF-C expression and secretion in human chondrosarcoma cells. The conditioned medium from adiponectin-treated cells significantly induced tube formation and migration of human lymphatic endothelial cells. In addition, adiponectin knock down inhibited lymphangiogenesis in vitro and in vivo We also found that adiponectin-induced VEGF-C is mediated by the calmodulin-dependent protein kinase II (CaMKII), AMP-activated protein kinase (AMPK) and p38 signaling pathway. Furthermore, the expression of miR-27b was negatively regulated by adiponectin via the CaMKII, AMPK and p38 cascade. The present study is the first to describe the mechanism of adiponectin-promoted lymphangiogenesis by up-regulating VEGF-C expression in chondrosarcomas. Thus, adiponectin could serve as a therapeutic target in chondrosarcoma metastasis and lymphangiogenesis.

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“…For example, miRNA (miR)-126, originally identified as an endothelial-specific miRNA playing an essential role in angiogenesis and vascular integrity, [9][10][11] has been shown to function as a critical tumor suppressor in various types of solid tumors. 5,[12][13][14][15][16][17][18][19] In contrast, we have shown that miR-126 is aberrantly overexpressed and likely plays an oncogenic role in core binding factor (CBF) leukemia. 20 CBF leukemia is characterized by the presence of a t(8;21)(q22;q22) or an inv(16)(p13.1q22) chromosomal rearrangement, which accounts for ;20% to 30% of primary acute myeloid leukemia (AML) cases.…”

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confidence: 99%

Overexpression and knockout of miR-126 both promote leukemogenesis

Chen

et al. 2015

Blood

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Key Points• Both overexpression and knockout of miR-126 result in enhanced leukemogenesis.• Overexpression and knockout of miR-126 activate distinct gene signaling and are associated with different biological consequences.It is generally assumed that gain-and loss-of-function manipulations of a functionally important gene should lead to the opposite phenotypes. We show in this study that both overexpression and knockout of microRNA (miR)-126 surprisingly result in enhanced leukemogenesis in cooperation with the t(8;21) fusion genes AML1-ETO/RUNX1-RUNX1T1 and AML1-ETO9a (a potent oncogenic isoform of AML1-ETO). In accordance with our observation that increased expression of miR-126 is associated with unfavorable survival in patients with t(8;21) acute myeloid leukemia (AML), we show that miR-126 overexpression exhibits a stronger effect on long-term survival and progression of AML1-ETO9a-mediated leukemia stem cells/leukemia initiating cells (LSCs/LICs) in mice than does miR-126 knockout. Furthermore, miR-126 knockout substantially enhances responsiveness of leukemia cells to standard chemotherapy. Mechanistically, miR-126 overexpression activates genes that are highly expressed in LSCs/LICs and/or primitive hematopoietic stem/progenitor cells, likely through targeting ERRFI1 and SPRED1, whereas miR-126 knockout activates genes that are highly expressed in committed, more differentiated hematopoietic progenitor cells, presumably through inducing FZD7 expression. Our data demonstrate that miR-126 plays a critical but 2-faceted role in leukemia and thereby uncover a new layer of miRNA regulation in cancer. Moreover, because miR-126 depletion can sensitize AML cells to standard chemotherapy, our data also suggest that miR-126 represents a promising therapeutic target. (Blood. 2015;126(17):2005-2015 Introduction MicroRNAs (miRNAs) have been implicated in the pathogenesis of various types of cancers. [1][2][3][4][5][6][7][8] Some miRNAs play distinct roles in different types of cancers. For example, miRNA (miR)-126, originally identified as an endothelial-specific miRNA playing an essential role in angiogenesis and vascular integrity, [9][10][11] has been shown to function as a critical tumor suppressor in various types of solid tumors. 5,[12][13][14][15][16][17][18][19] In contrast, we have shown that miR-126 is aberrantly overexpressed and likely plays an oncogenic role in core binding factor (CBF) leukemia. 20 CBF leukemia is characterized by the presence of a t(8;21)(q22;q22) or an inv(16)(p13.1q22) chromosomal rearrangement, which accounts for ;20% to 30% of primary acute myeloid leukemia (AML) cases. [21][22][23] The potential oncogenic role of miR-126 in AML was further confirmed by other groups. 24,25 However, it was reported that attenuation of miR-126 expression in normal hematopoietic stem/progenitor cells (HSPCs) resulted in expansion of long-term repopulating hematopoietic stem cells. 26 Thus, the definitive role of miR-126 in the hematopoietic system warrants further investigation.To precisely define ...

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Osteoblast-derived WISP-1 increases VCAM-1 expression and enhances prostate cancer metastasis by down-regulating miR-126

Cited by 51 publications

References 41 publications

Wnt2 and WISP-1/CCN4 Induce Intimal Thickening via Promotion of Smooth Muscle Cell Migration

Wnt2 and WISP-1/CCN4 Induce Intimal Thickening via Promotion of Smooth Muscle Cell Migration

Adiponectin promotes VEGF-C-dependent lymphangiogenesis by inhibiting miR-27b through a CaMKII/AMPK/p38 signaling pathway in human chondrosarcoma cells

Overexpression and knockout of miR-126 both promote leukemogenesis

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