Ras activation mediates WISP-1-induced increases in cell motility and matrix metalloproteinase expression in human osteosarcoma

Wu, Chien-Lin; Tsai, Hsiao‐Chi; Chen, Zhenwei; Wu, Chi‐Ming; Li, Te‐Mao; Fong, Yi‐Chin; Tang, Chih‐Hsin

doi:10.1016/j.cellsig.2013.09.005

Cited by 40 publications

(47 citation statements)

References 52 publications

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“…Even with early diagnosis and aggressive treatment, the prognosis for OS remains poor. Molecular mechanisms underlying disease progression remain poorly understood [2,3]. Therefore, a better understanding of the underlying mechanisms of human osteosarcoma development and progression, as well as identifying molecular targets, is necessary to find effective therapeutic interventions.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-375 functions as a tumor suppressor in osteosarcoma by targeting PIK3CA

Shi

Chu

et al. 2015

Tumor Biol.

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Osteosarcoma has become one of the most common primary malignant bone tumors in childhood and adult. Numerous studies have demonstrated that aberrant microRNA (miRNA) expression is involved in human disease including cancer. To date, the potential miRNAs regulating osteosarcoma growth and progression are not fully identified yet. Herein, we showed that miR-375 was frequently downregulated in osteosarcoma tissue and cell lines compared to normal human colon tissues. Overexpression of miR-375 resulted in decreased expression of PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha) at both mRNA and protein levels. We found that miR-375 overexpression markedly suppressed cell proliferation in vitro. And inhibition of miR-375 promotes osteosarcoma growth. Mechanistic studies showed that PIK3CA was a potential target of miR-375 and it mediated reduction of PIK3CA resulted in suppression of PI3K/Akt pathway. Taken together, our results demonstrate that miR-375 functions as a growth-suppressive miRNA and plays an important role in inhibiting the tumorigenesis through targeting PIK3CA in osteosarcoma.

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Section: Introductionmentioning

confidence: 99%

MicroRNA-375 functions as a tumor suppressor in osteosarcoma by targeting PIK3CA

Shi

Chu

et al. 2015

Tumor Biol.

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“…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). 16 WISP-1 is a member of the CCN family of genes, 17 which regulates fibrosis and wound healing, 18 angiogenesis, 19 osteogenesis, 20 and cancer. 21 In cultured VSMCs, WISP-1 promotes survival, 19 proliferation, 22 and migration through integrin α5β1.…”

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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“…cysteinerich protein 61 (CCN1) via αvβ3 [68], CCN3 via αvβ5 [69], and WISP1 (CCN4) via αvβ3 [70] to induce intracellular signaling events [2,8]. Integrins appear to regulate inflammatory responses such as TNF release [71].…”

Section: Wisp1 and Toll-like Receptor (Tlrs) Integrin-mediated Signamentioning

confidence: 99%

Research on WISP1 in Lung Disease

Zhang¹

2016

JACCOA

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Ras activation mediates WISP-1-induced increases in cell motility and matrix metalloproteinase expression in human osteosarcoma

Cited by 40 publications

References 52 publications

MicroRNA-375 functions as a tumor suppressor in osteosarcoma by targeting PIK3CA

MicroRNA-375 functions as a tumor suppressor in osteosarcoma by targeting PIK3CA

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

Research on WISP1 in Lung Disease

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