Daam1 activates RhoA to regulate Wnt5a‑induced glioblastoma cell invasion

Liu, Guiyang; Yan, Ting; Li, Xiaorong; Sun, Jianhui; Zhang, Bo; Wang, Hongjie; Zhu, Yichao

doi:10.3892/or.2017.6124

Cited by 25 publications

(37 citation statements)

References 34 publications

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“…Preincubation with CCG-1423 (1 μmol/L) completely inhibits the collagen-induced haptotaxis of breast MDA-MB-231 and MDA-MB-453 cancer cells 18. CCG-1423 (0.022 μmol/L) blocks Wnt5a-induced glioblastoma U251 and T98MG cell invasion 16. Here, we found that treatment with CCG-1423 (1 µmol/L) inhibited the cell invasion of ESCC KYSE410 and KYSE520 cells.…”

Section: Discussionmentioning

confidence: 54%

“…We previously found that Wnt5a stimulates the migration of breast cancer cells and promotes the invasion of glioblastoma cells via Rho signaling pathways 15,16,19. Liu et al reported that Wnt5a enhances the ability of cell mobility vi a RhoA signaling pathways in gastric cancer 23.…”

Section: Discussionmentioning

confidence: 95%

“…Wnt5a, as a nontransforming Wnt family member, mediates cancer initiation and metastasis 13,14. Previous studies found that Wnt5a triggers disheveled 2/disheveled-associated activator of morphogenesis 1 (DAAM1) signaling pathway and actives RhoA, resulting in the elevation of the migratory capacity of breast cancer cells and the invasion of glioblastoma cells 15,16. DAAM1, an element of cellular actin cytoskeleton, interacts with disheveled and RhoA and can polymerize actin filaments at the barbed end 13,15,17.…”

Section: Introductionmentioning

confidence: 99%

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<p>Wnt5a induces ROR1 and ROR2 to activate RhoA in esophageal squamous cell carcinoma cells</p>

Wu¹,

Yan²,

Hao³

et al. 2019

CMAR

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Background: Wnt5a is a nontransforming Wnt family member and identified as an oncogenic role on cell motility of breast cancer and glioblastoma. However, Wnt5a signaling in esophageal squamous cell carcinoma (ESCC) progression remains poorly defined. Materials and methods: Immunohistochemistry assays were used to measure the Wnt5a expression in ESCC sections. We evaluated the role of receptor tyrosine kinase-like orphan receptor (ROR)1/2 and RhoA on the invasion of ESCC cells by using cell invasion assay, immunoprecipitation, immunofluorescence, and Rho activation assay. Results: Wnt5a was highly expressed in invasive ESCC tissues compared with that in noninvasive and nonmalignant tissues. In vitro assay showed that sfrp2 (Wnt5a antagonist) largely blocked the invasion but not the colony formation of KYSE410 and KYSE520 ESCC cells. Anti-ROR1 mAb and ROR2-shRNA markedly inhibited the disheveled-associated activator of morphogenesis 1 (DAAM1) activity, RhoA activity, microfilament formation and the invasion of ESCC cells. Fluorescent phalloidin staining experiment showed ROR1/ROR2, receptors of Wnt5a signaling, and regulated the reassembly of actin filaments in ESCC cells. Further experiments showed that ROR1 was strongly associated with ROR2 in KYSE410 cells. The activation of RhoA, not Rac1 or Rac2, was involved in ROR1/ROR2 signaling pathway. By using DAAM1 shRNA, we found that RhoA was downstream of DAAM1, which could be rescued by the overexpression of wild-type DAAM1. This could be further proved by a RhoA inhibitor CCG-1423 which could inhibit the invasion of ESCC cells but not DAAM1 activity. Conclusions: Wnt5a promotes ESCC cell invasion via ROR1 and ROR2 receptors and DAAM1/RhoA signaling pathway.

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Section: Discussionmentioning

confidence: 54%

Section: Discussionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

<p>Wnt5a induces ROR1 and ROR2 to activate RhoA in esophageal squamous cell carcinoma cells</p>

Wu¹,

Yan²,

Hao³

et al. 2019

CMAR

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“…Twenty-nine glioblastoma cases were recruited from Jinan Fourth People’s Hospital and Linyi Central Hospital from 2015 to 2019. Glioblastoma was diagnosed according to World Health Organization (WHO) 2007 and 2016 histopathologic criteria [23]. All high-density glioblastoma tissues were histopathologically confirmed by 2 pathologists.…”

Section: Methodsmentioning

confidence: 99%

Tivantinib Hampers the Proliferation of Glioblastoma Cells via PI3K/Akt/Mammalian Target of Rapamycin (mTOR) Signaling

Wu¹,

Li²,

Zhang³

et al. 2019

Med Sci Monit

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BackgroundGlioblastoma, the most common and malignant glial tumor, often has poor prognosis. Tivantinib has shown its potential in treating c-Met-high carcinoma. No studies have explored whether tivantinib inhibits the development of glioblastoma.Material/MethodsThe correlation between c-Met expression and clinicopathological characteristics of glioblastoma was investigated. U251 and T98MG glioblastoma cells treated with tivantinib, PI3K inhibitor (LY294002), PI3K activator (740 Y-P), and/or mammalian target of rapamycin (mTOR) inhibitor were subjected to MTT assay or colony formation assay to evaluate cell proliferation. The expression of mTOR signaling and caspase-3 in tivantinib-treated glioblastoma cells was differentially measured by western blotting.ResultsIn a group of Chinese patients, expression of c-Met was elevated with the size of glioblastoma, but not with the other clinicopathological characteristics, including gender, age, grade, IDH status, 1p/19q status, and Ki67 status. High dose of tivantinib (1 μmol/L) obviously repressed the proliferation and colony formation of U251 and T98MG glioblastoma cells, but low dose (0.1 μmol/L) of tivantinib failed to retard cell proliferation. Tivantinib blocked PI3K/Akt/mTOR signaling but did not change the expression of cleaved caspase-3. PI3K activator 740 Y-P (20 μmol/L) significantly rescued tivantinib-induced decrease of cell proliferation. Tivantinib (1 μmol/L) in combination with PI3K inhibitor LY294002 (0.5 μmol/L) and mTOR inhibitor rapamycin (0.1 nmol/L) largely inhibited the proliferation of glioblastoma cells.Conclusionsc-MET inhibitor tivantinib blocks PIKE/Akt/mTOR signaling and hampers the proliferation of glioblastoma cells, which endows the drug a therapeutic effect.

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“…Furthermore, it has been described that transmembrane ion cotransporters induce cell migration and EMT through downstream activation of RHOA and RAC pathways [54]. Besides, several pathways including Wnt, PI3K/Akt, and ODZ1 have been shown to be associated with RhoA to regulate cytoskeletal changes that allows migration [55–57].…”

Section: The Molecular Hallmarks Of Invasion In Gbmmentioning

confidence: 99%

Molecular and Clinical Insights into the Invasive Capacity of Glioblastoma Cells

Velásquez

Mansouri

Mora

et al. 2019

Journal of Oncology

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The invasive capacity of GBM is one of the key tumoral features associated with treatment resistance, recurrence, and poor overall survival. The molecular machinery underlying GBM invasiveness comprises an intricate network of signaling pathways and interactions with the extracellular matrix and host cells. Among them, PI3k/Akt, Wnt, Hedgehog, and NFkB play a crucial role in the cellular processes related to invasion. A better understanding of these pathways could potentially help in developing new therapeutic approaches with better outcomes. Nevertheless, despite significant advances made over the last decade on these molecular and cellular mechanisms, they have not been translated into the clinical practice. Moreover, targeting the infiltrative tumor and its significance regarding outcome is still a major clinical challenge. For instance, the pre- and intraoperative methods used to identify the infiltrative tumor are limited when trying to accurately define the tumor boundaries and the burden of tumor cells in the infiltrated parenchyma. Besides, the impact of treating the infiltrative tumor remains unclear. Here we aim to highlight the molecular and clinical hallmarks of invasion in GBM.

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Daam1 activates RhoA to regulate Wnt5a‑induced glioblastoma cell invasion

Cited by 25 publications

References 34 publications

<p>Wnt5a induces ROR1 and ROR2 to activate RhoA in esophageal squamous cell carcinoma cells</p>

<p>Wnt5a induces ROR1 and ROR2 to activate RhoA in esophageal squamous cell carcinoma cells</p>

Tivantinib Hampers the Proliferation of Glioblastoma Cells via PI3K/Akt/Mammalian Target of Rapamycin (mTOR) Signaling

Molecular and Clinical Insights into the Invasive Capacity of Glioblastoma Cells

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