RILP suppresses invasion of breast cancer cells by modulating the activity of RalA through interaction with RalGDS

Wang, Z; Zhou, Yunhe; Hu, Xiaomin; Chen, W; Lin, Xue; Sun, Lixiang; Xu, Xiaolin; Hong, Wanjin; Wang, T

doi:10.1038/cddis.2015.266

Cited by 18 publications

(20 citation statements)

References 49 publications

(73 reference statements)

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“…Cell migration assay was performed using Transwell chambers with 8.0 μm pore membrane as described previously [ 28 ]. Briefly, after infection with LV-SHCBP1, LV-shSHCBP1, or LV-Control for 72 h, cells were harvested and resuspended in serum-free medium.…”

Section: Methodsmentioning

confidence: 99%

SHCBP1 promotes synovial sarcoma cell metastasis via targeting TGF-β1/Smad signaling pathway and is associated with poor prognosis

Peng

Zhao

Song

et al. 2017

J Exp Clin Cancer Res

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BackgroundOur previous studies reported that SHC SH2-domain binding protein 1 (SHCBP1) functions as an oncogene via promoting cell proliferations in synovial sarcoma (SS) cells. However, whether SHCBP1 has any effect on tumor metastasis remains unexplored.MethodsThe expression of SHCBP1 was analyzed in 76 SS tissues and two SS cell lines by immunohistochemistry and real-time RT-PCR. The relationship between SHCBP1 expression and the clinicopathological features of SS was investigated. The role of SHCBP1 in SS cell adhesion, migration, invasion and angiogenesis was explored by adhesion, Wound healing, Transwell, and Matrigel tube formation assays. Western blotting was conducted to detect the protein expressions of TGF-β1/Smad signaling pathway and EMT-related markers. The key molecules associated with migration, invasion and EMT were evaluated by immunohistochemistry in tumor specimens.ResultsIn current study, we demonstrated that SHCBP1 overexpression significantly enhanced adhesion, migration, invasion and angiogenesis of SS cells. In contrast, SHCBP1 knockdown elicited the opposite effects on these phenotypes in vitro. SHCBP1 promoted tumor metastasis through inducing epithelial-mesenchymal transition (EMT) in SS cells. SHCBP1 knockdown could block the incidence of metastasis and EMT in SS cells. Furthermore, transforming growth factor-β1 (TGF-β1) induced SHCBP1 expression in a time-dependent pattern and SHCBP1 knockdown inhibited TGF-β1-induced EMT. The activation of the TGF-β1/Smad signaling pathway was involved in the oncogenic functions of SHCBP1 in SS. In addition, high expression of SHCBP1 in SS patients was associated with tumor progression and decreased survival as well as poor prognosis.ConclusionsTaken together, our results indicate that SHCBP1 may promote the metastasis of SS by inducing EMT through targeting TGF-β1/Smad signaling pathway and can be a potential molecular target for SS therapy.

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Section: Methodsmentioning

confidence: 99%

SHCBP1 promotes synovial sarcoma cell metastasis via targeting TGF-β1/Smad signaling pathway and is associated with poor prognosis

Peng

Zhao

Song

et al. 2017

J Exp Clin Cancer Res

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“…It has been recently shown that RILP depletion in MCF7 (breast adenocarcinoma) cells causes a faster closure of the wound in wound-healing assay demonstrating a role of RILP in cell migration. 19 In order to better characterize this role of RILP and to investigate if this is restricted to breast cancer cells we performed a woundhealing assay on NCI H1299 (lung carcinoma) cells transfected with either control RNA or siRNA against RILP. Confluent monolayers of cells were scratched with a pipette tip and migrating cells were imaged at time intervals of 30 min over an 8-h time period.…”

Section: Resultsmentioning

confidence: 99%

“…19 Therefore, the effect of RILP silencing on cell velocity could be mediated by RalGDS. However, RalGDS does not interact with the mutated form of RILP, RILP-C33 that affects adhesion and spreading.…”

Section: Discussionmentioning

confidence: 99%

“… 17 , 18 Moreover, it has been recently demonstrated that RILP expression is lower in highly invasive cells and that RILP silencing promotes migration and invasion of breast cancer cells, whereas RILP overexpression suppresses migration. 19 Although it has been observed that RILP affects actin cytoskeleton by interacting with Ral guanine nucleotide dissociation stimulator (RalGDS), a regulator of RalA, 19 how RILP affects cell motility and other aspects of cell migration has not been studied.…”

Section: Introductionmentioning

confidence: 99%

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Characterization of the role of RILP in cell migration

et al. 2017

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Rab-interacting lysosomal protein (RILP) is a regulator of late stages of endocytosis. Recent work proved that depletion of RILP promotes migration of breast cancer cells in wound healing assay, whereas its overexpression influences re-arrangements of actin cytoskeleton. Here, we further characterized the role of RILP in cell migration by analyzing several aspects of this process. We showed that RILP is fundamental also for migration of lung cancer cells regulating cell velocity. RILP silencing did not affect Golgi apparatus nor microtubules reorientation during migration. However, both RILP over-expression and expression of its mutated form, RILPC33, impair cell adhesion and spreading. In conclusion, our results demonstrate that RILP has important regulatory roles in cell motility affecting migration velocity but also in cell adhesion and cell spreading.

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“…A comparison of BPA-vs. E2-treated cultures revealed alterations in extracellular matrix organization, glycolytic process, cell migration, and activation of Ral GTPase activity. Recently, RalA activity was shown to promote the invasion of breast cancer cells in vitro (22). All 10 of the biological processes affected by both Pht and PCB were defined by a single protein per process.…”

Section: Functional Classes Of Proteins and Pathways Changed By Exposmentioning

confidence: 99%

Quantitative proteomic analyses of mammary organoids reveals distinct signatures after exposure to environmental chemicals

Williams

Lemieux

Hassis

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Common environmental contaminants such as bisphenols and phthalates and persistent contaminants such as polychlorinated biphenyls are thought to influence tissue homeostasis and carcinogenesis by acting as disrupters of endocrine function. In this study we investigated the direct effects of exposure to bisphenol A (BPA), mono-n-butyl phthalate (Pht), and polychlorinated biphenyl 153 (PCB153) on the proteome of primary organotypic cultures of the mouse mammary gland. At low-nanomolar doses each of these agents induced distinct effects on the proteomes of these cultures. Although BPA treatment produced effects that were similar to those induced by estradiol, there were some notable differences, including a reduction in the abundance of retinoblastomaassociated protein and increases in the Rho GTPases Ras-related C3 botulinum toxin substrate 1 (Rac1) and cell division cycle protein CDC42. Both Pht and PCB153 induced changes that were distinct from those induced by estrogen, including decreased levels of the transcriptional corepressor C-terminal binding protein 1. Interestingly, the three chemicals appeared to alter the abundance of distinct splice forms of many proteins as well as the abundance of several proteins that regulate RNA splicing. Our combined results indicate that the three classes of chemical have distinct effects on the proteome of normal mouse mammary cultures, some estrogen-like but most estrogen independent, that influence diverse biological processes including apoptosis, cell adhesion, and proliferation.proteomics | mammary epithelium | environmental chemicals | organotypic culture | estrogen B reast cancers are caricatures of normal tissue development (1-3). The same underlying mechanisms that affect the cell processes needed for normal mammary development contribute to cancer progression. By affecting the distribution of interacting cells and communication among them through nontargeted effects, carcinogens can promote the outgrowth of altered cells with malignant potential. Exposure to environmental agents can affect mammary gland development and alter breast cancer risk. Epidemiologic studies have associated a number of environmental factors with increased breast cancer risk (4). Some of these factors may have low-level effects that are not genotoxic but alter immune responses, vascularity, or the microenvironment or that change susceptibility to carcinogens. A current weakness in models of cancer risk assessment is the lack of consideration of factors that influence the susceptibility of mixed cell populations to transformation. Indeed, ionizing radiation, the prototypical carcinogen, promotes changes in the biochemical properties in cultured mouse and human breast cells, in the stromal environment, and in intact mouse mammary gland (5-7).Physiologically relevant 3D culture models can recapitulate crucial aspects of the dynamic and reciprocal signaling necessary for establishing and maintaining tissue-specific morphogenetic programs. The determination of the molecular mechanisms underlying m...

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RILP suppresses invasion of breast cancer cells by modulating the activity of RalA through interaction with RalGDS

Cited by 18 publications

References 49 publications

SHCBP1 promotes synovial sarcoma cell metastasis via targeting TGF-β1/Smad signaling pathway and is associated with poor prognosis

SHCBP1 promotes synovial sarcoma cell metastasis via targeting TGF-β1/Smad signaling pathway and is associated with poor prognosis

Characterization of the role of RILP in cell migration

Quantitative proteomic analyses of mammary organoids reveals distinct signatures after exposure to environmental chemicals

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