WISP1 overexpression promotes proliferation and migration of human vascular smooth muscle cells via AKT signaling pathway

Lu, Shun; Líu, Hao; Lu, Lihe; Wan, Heng; Lin, Zhiqi; Qian, Kai; Yao, Xiang; Chen, Qing; Liu, Wenjun; Yan, Jianyun; Liu, Zhengjun

doi:10.1016/j.ejphar.2016.06.027

Cited by 27 publications

(25 citation statements)

References 39 publications

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“…In human glioblastoma, the WISP1-activated MEK/ ERK pathway might be responsible for the EMT of the tumor cells (44). The activation of various signaling, including PI3K/ AKT, MEK/ERK, NF-B, or JNK/p38 pathways, has been shown to be essential for WISP1-induced cell migration and/or invasion in vascular smooth muscle cells, cholangiocarcinoma, chondrosarcoma, oral squamous cell carcinoma, osteosarcoma, and colorectal cancer cells (30,33,34,(45)(46)(47)(48).…”

mentioning

confidence: 99%

WNT1-inducible signaling pathway protein 1 (WISP1/CCN4) stimulates melanoma invasion and metastasis by promoting the epithelial–mesenchymal transition

Deng

Fernández

McLaughlin

et al. 2019

Journal of Biological Chemistry

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Besides intrinsic changes, malignant cells also release soluble signals that reshape their microenvironment. Among these signals is WNT1-inducible signaling pathway protein 1 (WISP1), a secreted matricellular protein whose expression is elevated in several cancers, including melanoma, and is associated with reduced survival of patients diagnosed with primary melanoma. Here, we found that WISP1 knockout increases cell proliferation and represses wound healing, migration, and invasion of mouse and human melanoma cells in multiple in vitro assays. Metastasis assays revealed that WISP1 knockout represses tumor metastasis of B16F10 and YUMM1.7 melanoma cells in both C57BL/ 6Ncrl and NOD-scid IL2R␥ null (NSG) mice. WT B16F10 cells having an invasion phenotype in a transwell assay possessed a gene expression signature similar to that observed in the epithelial-mesenchymal transition (EMT), including E-cadherin repression and fibronectin and N-cadherin induction. Upon WISP1 knockout, expression of these EMT signature genes went in the opposite direction in both mouse and human cell lines, and EMT-associated gene expression was restored upon exposure to media containing WISP1 or to recombinant WISP1 protein. In vivo, Wisp1 knockout-associated metastasis repression was reversed by the reintroduction of either WISP1 or snail family transcriptional repressor 1 (SNAI1). Experiments testing EMT gene activation and inhibition with recombinant WISP1 or kinase inhibitors in B16F10 and YUMM1.7 cells suggested that WISP1 activates AKT Ser/Thr kinase and that MEK/ ERK signaling pathways shift melanoma cells from proliferation to invasion. Our results indicate that WISP1 present within the tumor microenvironment stimulates melanoma invasion and metastasis by promoting an EMT-like process.

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mentioning

confidence: 99%

WNT1-inducible signaling pathway protein 1 (WISP1/CCN4) stimulates melanoma invasion and metastasis by promoting the epithelial–mesenchymal transition

Deng

Fernández

McLaughlin

et al. 2019

Journal of Biological Chemistry

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“…Mucin 1 (MUC1) and WNT1 inducible signaling pathway protein 1 (WISP1) have been reported to inhibit E-cadherin-mediated cell-cell adhesion, induce the expression of transcription factors (Snail, N-cadherin, ZEB1 and Smad2), and in turn activate EMT in cancer cells [20, 21]. Combining the data of our microarray and verified PCR, we found that both MUC1 (Figure 5A, 5B) and WISP1 (Figure 5A, 5C) decreased after Talin-1 knockdown.…”

Section: Resultsmentioning

confidence: 99%

“…Overall, these data suggest that Talin-1 may promote cell adhesion via regulating the EMT process. Interestingly, WISP1 was also shown to promote tumor cell metastasis by activating PI3K/Akt/mTOR signaling [20, 21], which indicates that Talin-1 may promote cell adhesion via the classic mTOR pathway. Additionally, other PCR verified cell adhesion-related genes including SLAM family member 7 (SLAMF7) (Figure 5A, 5D), vitronectin (VTN) (Figure 5A, 5E), and fibrinogen beta chain (FGB) (Figure 5A, 5F) were also downregulated in the sh-Talin-1 group compared with the NC ( P = 0.0022, 0.0018 and 0.0002, respectively) and sh-mock ( P = 0.0002, 0.0070 and < 0.0001, respectively).…”

Section: Resultsmentioning

confidence: 99%

Talin-1 interaction network promotes hepatocellular carcinoma progression

et al. 2017

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Talin-1 is a known oncogene-associated protein. In this study, we set out to determine its role and mechanisms in hepatocellular carcinoma (HCC) progression. We found Talin-1 to be highly expressed in HCC cells relative to non-cancer liver epithelial cells and to promote tumor growth and metastasis. We used Whole Human Genome Oligo Microarray analysis with HCC cells and HCC cells in which Talin-1 was knocked down using shRNA to identify transcripts regulated by Talin-1. Of the 40,000 tested genes, 3099 were differentially expressed after Talin-1 knockdown; expression of 1924 genes was increased, while expression of 2175 was decreased. Gene ontology (GO) profiling indicated that Talin-1 promotes many HCC progression-related activities, including ion transport and membrane depolarization, cell growth, and cell adhesion. We also characterized the network of gene transcripts regulated by Talin-1 and their role in promoting HCC progression. Our findings confirm the role of Talin-1 in carcinogenesis and provided a set of novel therapeutic targets for the treatment of HCC.

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“…In regard to PI 3-K and Akt, Akt is activated during increased WISP1 expression under conditions of cell injury such as during DNA damage, mechanical strain in osteoblasts, fibroblast proliferation in airway remodeling, cardiomyocyte injury vascular smooth muscle proliferation (Lu et al 2016), oxidative stress, and Ab exposure (Shang et al 2013). Once Akt is activated, WISP1 phosphorylates and inhibits GSK-3b that prevents b-catenin from becoming phosphorylated, ubiquinated, and degraded.…”

Section: Signaling Pathways Of Wisp1mentioning

confidence: 99%

“…WISP1 can improve cardiomyocyte survival (Shanmugam et al 2011) and prevents cardiomyocyte cell death through PI3-K, Akt, and survivin pathways. WISP1 leads to vascular smooth muscle proliferation that may be important for tissue repair during injury but also may negatively impact restenosis following vascular grafting (Lu et al 2016). However, WISP1 does not appear to lead to cellular proliferation in aging vascular cells.…”

Section: Wisp1 In Cellular Repair and Proliferationmentioning

confidence: 99%

WISP1i

2018

Encyclopedia of Signaling Molecules

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WISP1 overexpression promotes proliferation and migration of human vascular smooth muscle cells via AKT signaling pathway

Cited by 27 publications

References 39 publications

WNT1-inducible signaling pathway protein 1 (WISP1/CCN4) stimulates melanoma invasion and metastasis by promoting the epithelial–mesenchymal transition

WNT1-inducible signaling pathway protein 1 (WISP1/CCN4) stimulates melanoma invasion and metastasis by promoting the epithelial–mesenchymal transition

Talin-1 interaction network promotes hepatocellular carcinoma progression

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