Targeting of NHERF1 through RNA interference inhibits the proliferation and migration of metastatic prostate cancer cells

Ma, Qiang; Jiao, Yanna; Hao, Yushu; Yan, Shanshan; Lyu, Nenan; Gao, Honglin; Li, Deguan; Liu, Qiang; Zheng, Junfang; Song, Ning

doi:10.3892/ol.2015.4007

Cited by 9 publications

(5 citation statements)

References 18 publications

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“…Regarding NHERF-1, this scaffolding protein has been involved in both tumor progression and inhibition in different types of cancer [20,[32][33][34][36][37][38][39][40][41][42][43][44][45][46]. Our data show a decrease in NHERF-1 immunolabeling in primary human prostate tumors compared to control samples.…”

Section: Discussionmentioning

confidence: 56%

“…Stabilization of β-catenin at cellular junctions in murine embryonic fibroblast models is also potentially induced by NHERF-1 [ 39 ]. Although these features are indicative of a tumor suppressor function, NHERF-1 has been involved in both tumor progression and inhibition [ 20 , 32 , 33 , 34 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 ]. An immunohistochemical study in prostatic cancer has revealed decreased NHERF-1 presence in primary and metastatic prostatic adenocarcinoma samples [ 20 ].…”

Section: Introductionmentioning

confidence: 99%

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MINDIN Exerts Protumorigenic Actions on Primary Prostate Tumors via Downregulation of the Scaffold Protein NHERF-1

Álvarez-Carrión

Gutiérrez‐Rojas

Ardura

et al. 2021

Cancers

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Advanced prostate cancer preferential metastasis to bone is associated with osteomimicry. MINDIN is a secreted matrix protein upregulated in prostate tumors that overexpresses bone-related genes during prostate cancer progression. Na+/H+ exchanger regulatory factor (NHERF-1) is a scaffold protein that has been involved both in tumor regulation and osteogenesis. We hypothesize that NHERF-1 modulation is a mechanism used by MINDIN to promote prostate cancer progression. We analyzed the expression of NHERF-1 and MINDIN in human prostate samples and in a premetastatic prostate cancer mouse model, based on the implantation of prostate adenocarcinoma TRAMP-C1 (transgenic adenocarcinoma of the mouse prostate) cells in immunocompetent C57BL/6 mice. The relationship between NHERF-1 and MINDIN and their effects on cell proliferation, migration, survival and osteomimicry were evaluated. Upregulation of MINDIN and downregulation of NHERF-1 expression were observed both in human prostate cancer samples and in the TRAMP-C1 model. MINDIN silencing restored NHERF-1 expression to control levels in the mouse model. Stimulation with MINDIN reduced NHERF-1 expression and triggered its mobilization from the plasma membrane to the cytoplasm in TRAMP-C1 cells. MINDIN-dependent downregulation of NHERF-1 promoted tumor cell migration and proliferation without affecting osteomimicry and adhesion. We propose that MINDIN downregulates NHERF-1 expression leading to promotion of processes involved in prostate cancer progression.

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Section: Discussionmentioning

confidence: 56%

Section: Introductionmentioning

confidence: 99%

MINDIN Exerts Protumorigenic Actions on Primary Prostate Tumors via Downregulation of the Scaffold Protein NHERF-1

Álvarez-Carrión

Gutiérrez‐Rojas

Ardura

et al. 2021

Cancers

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“…EBP50 has various roles in cellular functions of cancer cells, in addition to modulating transporter activity. For example, EBP50 affects cellular proliferation and trafficking [ 16 , 17 ], and oncogene activation [ 18 ]. Therefore, inhibiting EBP50 may have additional effects on cancer cells, depending on their type.…”

Section: Discussionmentioning

confidence: 99%

NHERF1/EBP50 as a Target for Modulation of MRP Function in HepG2 Cells

et al. 2021

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As increased expression and activities of efflux transporters (ETs) often cause drug resistance in cancers, we tried modulating ET activity in cancer cells, using scaffold proteins such as ezrin/radixin/moesin (ERM) proteins, and Na+/H+ exchanger regulatory factor-1 (NHERF1)/ERM-binding phosphoprotein of 50 kDa (EBP50). To see whether EBP50 modulated ET activities in human liver cancer HepG2 cells, we used EBP50 siRNA and a designed TAT-PDZ1 peptide. The EBP50 knockdown (EBP50KD) cells had significantly higher intracellular accumulations of Rho123 and carboxy-dichlorofluorescein (CDF), but not H33342 (i.e., the respective substrates of P-glycoprotein (P-gp), multidrug resistance-associated protein (MRP), and breast cancer resistance protein (BCRP)), compared with control HepG2, suggesting that EBP50 knockdown in HepG2 cells decreased activity of P-gp and MRP but not BCRP. Treatment with TAT-PDZ1 peptide (> 1 pM) resulted in significantly higher CDF accumulation in HepG2 cells, which persisted for ≥180 min after TAT-PDZ1 peptide treatment. These results imply that EBP50 can modulate ET activities. To our knowledge, this is the first report on using a competitive peptide to modulate interactions between MRP and EBP50.

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“…Extracellular leucine rich repeat and fibronectin type III domain-containing 2/protein phosphatase 1 regulatory subunit 29 putative oncogene, hypomethylation gene [113] overexpressed in GC tissues and cell lines [114]; oncogene in GBM [113] AT interacts with AurkA and eukaryotic translation initiation factor 2 subunit alpha (EIF2α) and regulates the kinase activity of AurkA to promote cell autophagy [113] knockdown inhibits cell proliferation, migration, invasion, increases E-cadherin and decreases N-cadherin [114] SLC9AR1/ NHERF1/ERB50 Solute carrier (SLC) family 9 (Na(+)/H(+) exchanger), member 3 regulator 1/sodium-hydrogen exchanger regulatory factor 1/ERM-binding phosphoprotein multifunctional cytoplasmic adaptor involved in growth factor signaling [115]; interacts with several proteins related to the estrogen pathway and tumorigenesis: EGFR, PTEN, PDGFR, beta catenin, EZR [116] in BC acts as a tumor suppressor protein; oncogene in glioma and other cancers; overexpressed in PCa tissue and cell lines [117] AT/PT MTORC1_SIGNALING; ESTROGEN_RESPONSE_LATE; downregulation is associated with Wnt/β-catenin inactivation [118]; knockdown enhances PDGF-induced cytoskeletal rearrangements and chemotactic migration of cells [119]; AKT-associated protein [115] knockdown suppresses proliferation and migration of metastatic PCa cells and promotes apoptosis [117] LGG-low grade glioma; LSCC-lung squamous cell carcinoma; LUAD-lung adenocarcinoma; LUSC-lung squamous cell carcinoma; MAPK-mitogen-activated protein kinase; MDM2-mouse double minute 2 homolog/E3 ubiquitin-protein ligase; MM-malignant mesothelioma; MMP9-metalloproteinase 9; mTOR-mammalian target of rapamycin; NOX1-NADPH oxidase 1; NPC-nasopharyngeal carcinoma; NSCLC-non-small-celllung cancer; OCCC-ovarian clear cell carcinoma; OSCC-oral squamous cell carcinoma; OXPHOS-oxidative phosphorylation pathway; PCC-pancreatic cancer; PCa-prostate cancer; PDAC-pancreatic ductal adenocarcinoma; PT-pro-tumorigenic; PTEN-phosphatase and tensin homolog; ROS-reactive oxygen species pathway; TC-testicular cancer; TCA-tricarboxylic acid; TGF-β-transforming growth factor beta; uLMS-uterine leiomyosarcoma; UPR-unfolded protein response; VIM-vimentin.…”

Section: Nckap1/nap1mentioning

confidence: 99%

Two-Dimensional-PAGE Coupled with nLC-MS/MS-Based Identification of Differentially Expressed Proteins and Tumorigenic Pathways in MCF7 Breast Cancer Cells Transfected for JTB Protein Silencing

Jayathirtha,

Jayaweera,

Whitham

et al. 2023

Molecules

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The identification of new cancer-associated genes/proteins, the characterization of their expression variation, the interactomics-based assessment of differentially expressed genes/proteins (DEGs/DEPs), and understanding the tumorigenic pathways and biological processes involved in BC genesis and progression are necessary and possible by the rapid and recent advances in bioinformatics and molecular profiling strategies. Taking into account the opinion of other authors, as well as based on our own team’s in vitro studies, we suggest that the human jumping translocation breakpoint (hJTB) protein might be considered as a tumor biomarker for BC and should be studied as a target for BC therapy. In this study, we identify DEPs, carcinogenic pathways, and biological processes associated with JTB silencing, using 2D-PAGE coupled with nano-liquid chromatography tandem mass spectrometry (nLC-MS/MS) proteomics applied to a MCF7 breast cancer cell line, for complementing and completing our previous results based on SDS-PAGE, as well as in-solution proteomics of MCF7 cells transfected for JTB downregulation. The functions of significant DEPs are analyzed using GSEA and KEGG analyses. Almost all DEPs exert pro-tumorigenic effects in the JTBlow condition, sustaining the tumor suppressive function of JTB. Thus, the identified DEPs are involved in several signaling and metabolic pathways that play pro-tumorigenic roles: EMT, ERK/MAPK, PI3K/AKT, Wnt/β-catenin, mTOR, C-MYC, NF-κB, IFN-γ and IFN-α responses, UPR, and glycolysis/gluconeogenesis. These pathways sustain cancer cell growth, adhesion, survival, proliferation, invasion, metastasis, resistance to apoptosis, tight junctions and cytoskeleton reorganization, the maintenance of stemness, metabolic reprogramming, survival in a hostile environment, and sustain a poor clinical outcome. In conclusion, JTB silencing might increase the neoplastic phenotype and behavior of the MCF7 BC cell line. The data is available via ProteomeXchange with the identifier PXD046265.

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Targeting of NHERF1 through RNA interference inhibits the proliferation and migration of metastatic prostate cancer cells

Cited by 9 publications

References 18 publications

MINDIN Exerts Protumorigenic Actions on Primary Prostate Tumors via Downregulation of the Scaffold Protein NHERF-1

MINDIN Exerts Protumorigenic Actions on Primary Prostate Tumors via Downregulation of the Scaffold Protein NHERF-1

NHERF1/EBP50 as a Target for Modulation of MRP Function in HepG2 Cells

Two-Dimensional-PAGE Coupled with nLC-MS/MS-Based Identification of Differentially Expressed Proteins and Tumorigenic Pathways in MCF7 Breast Cancer Cells Transfected for JTB Protein Silencing

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