当前位置： SCI文献检索 > CANCER RESEARCH期刊下所有文献 > Chemotherapy-Induced Extracellular Vesicle miRNAs Promote Breast Cancer Stemness by Targeting ONECUT2.

Chemotherapy-Induced Extracellular Vesicle miRNAs Promote Breast Cancer Stemness by Targeting ONECUT2.

Abstract：

:Cancer-secreted, extracellular vesicle (EV)-encapsulated miRNAs enable cancer cells to communicate with each other and with noncancerous cells in tumor pathogenesis and response to therapies. Here, we show that treatment with a sublethal dose of chemotherapeutic agents induces breast cancer cells to secrete EV with the capacity to stimulate a cancer stem-like cell (CSC) phenotype, rendering cancer cells resistance to therapy. Chemotherapy induced breast cancer cells to secrete multiple EV miRNAs, including miR-9-5p, miR-195-5p, and miR-203a-3p, which simultaneously targeted the transcription factor One Cut Homeobox 2 (ONECUT2), leading to induction of CSC traits and expression of stemness-associated genes, including NOTCH1, SOX9, NANOG, OCT4, and SOX2. Inhibition of these miRNAs or restoration of ONECUT2 expression abolished the CSC-stimulating effect of EV from chemotherapy-treated cancer cells. In mice bearing xenograft mammary tumors, docetaxel treatment caused elevations of miR-9-5p, miR-195-5p, and miR-203a-3p in circulating EV and decreased ONECUT2 expression and increased levels of stemness-associated genes. These effects following chemotherapy were diminished in tumors deficient in exosome secretion. In human breast tumors, neoadjuvant chemotherapy decreased ONECUT2 expression in tumor cells. Our results indicate a mechanism by which cancer cells communicate with each other and self-adapt to survive in response to cytotoxic treatment. Targeting these adaptation mechanisms along with chemotherapy, such as by blocking the EV miRNA-ONECUT2 axis, represents a potential strategy to maximize the anticancer effect of chemotherapy and to reduce chemoresistance in cancer management. SIGNIFICANCE: These findings reveal a critical mechanism of resistance to chemotherapy by which breast cancer cells secrete miRNA-containing extracellular vesicles to stimulate cancer stem cell-like features.

journal_name

Cancer Res

journal_title

Cancer research

authors

Shen M,Dong C,Ruan X,Yan W,Cao M,Pizzo D,Wu X,Yang L,Liu L,Ren X,Wang SE

doi

10.1158/0008-5472.CAN-18-4055

subject

Has Abstract

pub_date

2019-07-15 00:00:00

pages

3608-3621

issue

14

eissn

0008-5472

issn

1538-7445

pii

0008-5472.CAN-18-4055

journal_volume

79

pub_type

杂志文章

相关文献

CANCER RESEARCH文献大全
  • Vascular endothelial growth factor receptor-3 and focal adhesion kinase bind and suppress apoptosis in breast cancer cells.

    abstract：:Focal adhesion kinase (FAK) and vascular endothelial growth factor receptor-3 (VEGFR-3) are protein tyrosine kinases that are overexpressed in human cancer and play an important role in survival signaling. In addition to its involvement with cell survival, VEGFR-3 is a primary factor in lymphatic angiogenesis. Because...

    journal_title：Cancer research

    pub_type： 杂志文章

    doi：10.1158/0008-5472.CAN-05-1661

    authors： Garces CA,Kurenova EV,Golubovskaya VM,Cance WG

    更新日期：2006-02-01 00:00:00

  • Importance of tumor-specific cytotoxic CD8+ T-cells in eradication of a large subcutaneous MOPC-315 tumor following low-dose melphalan therapy.

    abstract：:We have previously demonstrated that depletion of CD8+ T-cells by the use of a monoclonal anti-Lyt-2.2 antibody abolishes the curative effectiveness of low-dose melphalan (L-phenylalanine mustard; L-PAM) therapy for BALB/c mice bearing a large (greater than or equal to 20 mm) s.c. MOPC-315 tumor and extensive metastas...

    journal_title：Cancer research

    pub_type： 杂志文章

    doi：

    authors： Takesue BY,Pyle JM,Mokyr MB

    更新日期：1990-12-01 00:00:00

  • The tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone is an active transplacental carcinogen in Syrian golden hamsters.

    abstract：:The tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is a potent carcinogen in adult laboratory rodents. Our previous studies have shown that NNK crosses the placenta in pregnant hamsters and is metabolized into DNA-methylating and clastogenic intermediates by fetal respiratory tract t...

    journal_title：Cancer research

    pub_type： 杂志文章

    doi：

    authors： Correa E,Joshi PA,Castonguay A,Schüller HM

    更新日期：1990-06-01 00:00:00

  • Binding characteristics and antitumor properties of 1A10 bispecific antibody recognizing gp40 and human transferrin receptor.

    abstract：:The bispecific murine monoclonal antibody (MAb) 1A10 has specificity for the human transferrin receptor (TfR) and the human tumor-associated antigen gp40. This antibody, therefore, functions as an "antigen fork" by binding to two distinct antigens on the same malignant cell. Highly purified 1A10 inhibits the growth of...

    journal_title：Cancer research

    pub_type： 杂志文章

    doi：

    authors： Amoroso AR,Clark JI,Litwin S,Hsieh-Ma S,Shi T,Alpaugh RK,Adams GP,Wolf EJ,Ring DB,Weiner LM

    更新日期：1996-01-01 00:00:00

  • Siah proteins: novel drug targets in the Ras and hypoxia pathways.

    abstract：:The Siah (seven in absentia homolog) family of RING-domain proteins are components of ubiquitin ligase complexes, targeting proteins for proteasomal degradation. Siah family members have been reported to function in Ras, estrogen, DNA-damage, and hypoxia response pathways. Although earlier reports implicated Siah prot...

    journal_title：Cancer research

    pub_type： 杂志文章,评审

    doi：10.1158/0008-5472.CAN-09-1676

    authors： House CM,Möller A,Bowtell DD

    更新日期：2009-12-01 00:00:00

  • Identification of an epitope region of the human proliferation-associated nucleolar antigen P120.

    abstract：:An epitope region, located at amino acid residues 173-180 (EAAA-GIQW), of a human cell proliferation-associated nucleolar antigen, P120, has been defined by mutational analysis and competition assays. A synthetic peptide corresponding to this epitope region completely blocks the binding of the anti-P120 antibody to Es...

    journal_title：Cancer research

    pub_type： 杂志文章

    doi：

    authors： Valdez BC,Busch RK,Larson RG,Busch H

    更新日期：1990-05-01 00:00:00

  • Akt SUMOylation regulates cell proliferation and tumorigenesis.

    abstract：:Proto-oncogene Akt plays essential roles in cell proliferation and tumorigenesis. Full activation of Akt is regulated by phosphorylation, ubiquitination, and acetylation. Here we report that SUMOylation of Akt is a novel mechanism for its activation. Systematically analyzing the role of lysine residues in Akt activati...

    journal_title：Cancer research

    pub_type： 杂志文章

    doi：10.1158/0008-5472.CAN-13-0538

    authors： Li R,Wei J,Jiang C,Liu D,Deng L,Zhang K,Wang P

    更新日期：2013-09-15 00:00:00

  • Inhibition of transformation of primary rat tracheal epithelial cells by retinoic acid.

    abstract：:The effect of retinoic acid (RA) on N-methyl-N'-nitro-N-nitrosoguanidine-induced transformation of primary cultures of rat tracheal epithelial cells was investigated. RA inhibited transformation of rat tracheal epithelial cells by up to 95% at concentrations of 3.3 to 33 nM which did not substantially affect cell surv...

    journal_title：Cancer research

    pub_type： 杂志文章

    doi：

    authors： Mass MJ,Nettesheim P,Beeman DK,Barrett JC

    更新日期：1984-12-01 00:00:00

  • Contribution of glutathione transferase M3-3 to 1,3-bis(2-chloroethyl)-1-nitrosourea resistance in a human non-small cell lung cancer cell line.

    abstract：:The glutathione transferase (GST) isoenzyme profile was determined in two human tumor cell lines, U1690 derived from a small cell lung cancer and U1810 derived from a non-small cell lung cancer. U1810 cells are 3.2-fold more resistant to 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) than are U1690 cells, a finding ascri...

    journal_title：Cancer research

    pub_type： 杂志文章

    doi：

    authors： Berhane K,Hao XY,Egyházi S,Hansson J,Ringborg U,Mannervik B

    更新日期：1993-09-15 00:00:00

  • A prospective study of meat and fat intake in relation to small intestinal cancer.

    abstract：:Diets high in red and processed meats are associated with carcinogenesis of the large intestine, but no prospective study has examined meat and fat intake in relation to cancer of the small intestine. We prospectively investigated meat and fat intakes, estimated from a food frequency questionnaire, in relation to smal...

    journal_title：Cancer research

    pub_type： 杂志文章

    doi：10.1158/0008-5472.CAN-08-2015

    authors： Cross AJ,Leitzmann MF,Subar AF,Thompson FE,Hollenbeck AR,Schatzkin A

    更新日期：2008-11-15 00:00:00

  • Drug Sensitivity and Allele Specificity of First-Line Osimertinib Resistance EGFR Mutations.

    abstract：:Osimertinib, a mutant-specific third-generation EGFR tyrosine kinase inhibitor, is emerging as the preferred first-line therapy for EGFR-mutant lung cancer, yet resistance inevitably develops in patients. We modeled acquired resistance to osimertinib in transgenic mouse models of EGFRL858R -induced lung adenocarcinoma...

    journal_title：Cancer research

    pub_type： 杂志文章

    doi：10.1158/0008-5472.CAN-19-3819

    authors： Starrett JH,Guernet AA,Cuomo ME,Poels KE,van Alderwerelt van Rosenburgh IK,Nagelberg A,Farnsworth D,Price KS,Khan H,Ashtekar KD,Gaefele M,Ayeni D,Stewart TF,Kuhlmann A,Kaech SM,Unni AM,Homer R,Lockwood WW,Michor F,G

    更新日期：2020-05-15 00:00:00

  • Sp3, but not Sp1, mediates the transcriptional activation of the p21/WAF1/Cip1 gene promoter by histone deacetylase inhibitor.

    abstract：:We previously reported that both sodium butyrate and trichostatin A (TSA), both of which are known as inhibitors of histone deacetylase, arrest human tumor cells at G1 and G2-M and activate the cyclin-dependent kinase inhibitor, the p21/WAF1/Cip1 gene promoter, through the Sp1 sites. In this study, we identified Sp1 a...

    journal_title：Cancer research

    pub_type： 杂志文章

    doi：

    authors： Sowa Y,Orita T,Minamikawa-Hiranabe S,Mizuno T,Nomura H,Sakai T

    更新日期：1999-09-01 00:00:00

  • Tumor-derived osteopontin suppresses antitumor immunity by promoting extramedullary myelopoiesis.

    abstract：:Extramedullary myelopoiesis occurs commonly in tumor-bearing animals and is known to lead to accumulation of peripheral myeloid-derived suppressor cells (MDSC), which play an important role in immune escape. However, the cellular and molecular mechanisms by which tumors induce extramedullary myelopoiesis are poorly un...

    journal_title：Cancer research

    pub_type： 杂志文章

    doi：10.1158/0008-5472.CAN-14-1482

    authors： Kim EK,Jeon I,Seo H,Park YJ,Song B,Lee KA,Jang Y,Chung Y,Kang CY

    更新日期：2014-11-15 00:00:00

  • Myeloid IKKβ promotes antitumor immunity by modulating CCL11 and the innate immune response.

    abstract：:Myeloid cells are capable of promoting or eradicating tumor cells and the nodal functions that contribute to their different roles are still obscure. Here, we show that mice with myeloid-specific genetic loss of the NF-κB pathway regulatory kinase IKKβ exhibit more rapid growth of cutaneous and lung melanoma tumors. I...

    journal_title：Cancer research

    pub_type： 杂志文章

    doi：10.1158/0008-5472.CAN-14-1091

    authors： Yang J,Hawkins OE,Barham W,Gilchuk P,Boothby M,Ayers GD,Joyce S,Karin M,Yull FE,Richmond A

    更新日期：2014-12-15 00:00:00

  • Successful treatment with DL-alpha-difluoromethylornithine in established human small cell variant lung carcinoma implants in athymic mice.

    abstract：:We report that p.o. administration of DL-alpha-difluoromethylornithine (DFMO), a specific inhibitor of polyamine biosynthesis, markedly inhibits the growth of established implants of cultured human small cell lung carcinoma (SCC) in athymic (nude) mice. Human SCC tumor cells, from a cell line which exhibited cell deat...

    journal_title：Cancer research

    pub_type： 杂志文章

    doi：

    authors： Luk GD,Abeloff MD,Griffin CA,Baylin SB

    更新日期：1983-09-01 00:00:00

  • Antisense DNA inhibition of tumor growth induced by c-Ha-ras oncogene in nude mice.

    abstract：:Antisense DNA has shown an ability to target specific oncogene transcripts and inhibit their expression in cells, but the degree to which sustained treatment can suppress total levels of an oncogenic product and alter tumorigenesis in vivo remains to be determined. In this study, NIH-3T3 cells transformed by the activ...

    journal_title：Cancer research

    pub_type： 杂志文章

    doi：

    authors： Gray GD,Hernandez OM,Hebel D,Root M,Pow-Sang JM,Wickstrom E

    更新日期：1993-02-01 00:00:00

  • Anti-alphav integrin monoclonal antibody intetumumab enhances the efficacy of radiation therapy and reduces metastasis of human cancer xenografts in nude rats.

    abstract：:We previously reported that intetumumab (CNTO 95), a fully human anti-αv integrin monoclonal antibody, is a radiosensitizer in mice with xenograft tumors. Because intetumumab does not cross-react with mouse integrins, but has cross-reactivity with rat integrins, we next studied the potential combined use of radiation ...

    journal_title：Cancer research

    pub_type： 杂志文章

    doi：10.1158/0008-5472.CAN-10-1639

    authors： Ning S,Tian J,Marshall DJ,Knox SJ

    更新日期：2010-10-01 00:00:00

  • Combined growth-inhibitory responses and ultrastructural alterations produced by 1,3-bis(2-chloroethyl)-1-nitrosourea and dexamethasone in rat glioma cell cultures.

    abstract：:The effect of 0.0001 to 10 muM 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and 1 muM dexamethasone on cell proliferation was studied by measuring cell densities in control and drug-treated rat glioma (strain C6) monolayer cultures. When C6 cultures were exposed to 0.01 to 10 muM BCNU, the growth rates decreased for 2 ...

    journal_title：Cancer research

    pub_type： 杂志文章

    doi：

    authors： Grasso RJ,Johnson CE,Boler RK,Moore NA

    更新日期：1977-02-01 00:00:00

  • Increasing c-FMS (CSF-1 receptor) expression decreases retinoic acid concentration needed to cause cell differentiation and retinoblastoma protein hypophosphorylation.

    abstract：:Increasing the expression of c-FMS (colony-stimulating factor 1 receptor) by introduction of a transgene reduced the concentration of retinoic acid or 1,25-dihydroxy vitamin D3 needed to cause myeloid or monocytic cell differentiation and hypophosphorylation of the retinoblastoma tumor suppressor protein (RB) typicall...

    journal_title：Cancer research

    pub_type： 杂志文章

    doi：

    authors： Yen A,Sturgill R,Varvayanis S

    更新日期：1997-05-15 00:00:00

  • Autotaxin hydrolyzes sphingosylphosphorylcholine to produce the regulator of migration, sphingosine-1-phosphate.

    abstract：:Autotaxin (ATX) is an exoenzyme that potently induces tumor cell motility, and enhances experimental metastasis and angiogenesis. ATX was shown recently to be identical to serum lysophospholipase D activity, producing lysophosphatidic acid (LPA) from lyso-glycerophospholipids. LPA, itself a strong chemoattractant for ...

    journal_title：Cancer research

    pub_type： 杂志文章

    doi：

    authors： Clair T,Aoki J,Koh E,Bandle RW,Nam SW,Ptaszynska MM,Mills GB,Schiffmann E,Liotta LA,Stracke ML

    更新日期：2003-09-01 00:00:00

  • TSP50 encodes a testis-specific protease and is negatively regulated by p53.

    abstract：:Earlier studies suggested that TSP50 is a testis-specific gene that encodes a protein, which is homologous to serine proteases but differs in that threonine replaces serine in its catalytic triad. Most importantly, it was abnormally reactivated in many breast cancer biopsies tested. While further investigating its bio...

    journal_title：Cancer research

    pub_type： 杂志文章

    doi：10.1158/0008-5472.CAN-06-3688

    authors： Xu H,Shan J,Jurukovski V,Yuan L,Li J,Tian K

    更新日期：2007-02-01 00:00:00

  • Chicken fetal and adult antigen expression on erythroleukemia cells before and after induced differentiation.

    abstract：:Avian erythroblastosis virus strain R (AEV)-transformed, cloned erythroleukemia cells from three different ages of SC strain chickens were analyzed before and after differentiation induced by 1.0 mM butyric acid for expression of chicken fetal antigens (CFAs) and chicken adult antigens (CAAs) and for hemoglobin expres...

    journal_title：Cancer research

    pub_type： 杂志文章

    doi：

    authors： Nelson CH,Allison JP,Kline K,Sanders BG

    更新日期：1982-11-01 00:00:00

  • CCL2/CCR2-dependent recruitment of functional antigen-presenting cells into tumors upon chemotherapy.

    abstract：:The therapeutic efficacy of anthracyclines relies, at least partially, on the induction of a dendritic cell- and T-lymphocyte-dependent anticancer immune response. Here, we show that anthracycline-based chemotherapy promotes the recruitment of functional CD11b(+)CD11c(+)Ly6C(high)Ly6G(-)MHCII(+) dendritic cell-like an...

    journal_title：Cancer research

    pub_type： 杂志文章

    doi：10.1158/0008-5472.CAN-13-1265

    authors： Ma Y,Mattarollo SR,Adjemian S,Yang H,Aymeric L,Hannani D,Portela Catani JP,Duret H,Teng MW,Kepp O,Wang Y,Sistigu A,Schultze JL,Stoll G,Galluzzi L,Zitvogel L,Smyth MJ,Kroemer G

    更新日期：2014-01-15 00:00:00

  • Paracrine stimulation of polarized secretion from monolayers of a neoplastic prostatic epithelial cell line by prostatic stromal cell proteins.

    abstract：:The paracrine influence of prostatic stromal cell proteins on a neoplastic prostate cell line (PA-III) was investigated. We have utilized an in vitro experimental model whereby confluent epithelial sheets of PA-III cells are grown on Matrigel-coated filters in bicameral chambers (Millicell-HA). Confluence of the epith...

    journal_title：Cancer research

    pub_type： 杂志文章

    doi：

    authors： Djakiew D,Tarkington MA,Lynch JH

    更新日期：1990-03-15 00:00:00

  • In vivo and in vitro pharmacological studies of aminoglutethimide as an aromatase inhibitor.

    abstract：:Use of steroid biosynthesis inhibitors to suppress estrogen production is a logical strategy in the treatment of women with hormone-dependent breast cancer. The clinical availability of aminoglutethimide as an inhibitor of cytochrome P-450-mediated steroid hydroxylations prompted study of the precise pharmacological a...

    journal_title：Cancer research

    pub_type： 杂志文章

    doi：

    authors： Santen RJ,Santner SJ,Tilsen-Mallett N,Rosen HR,Samojlik E,Veldhuis JD

    更新日期：1982-08-01 00:00:00

  • DNA synthesis inpermeable mouse ascites sarcoma cells.

    abstract：:DNA synthesis was studied in mouse ascites sarcoma cells using a permeable cell system. The sarcoma was induced by the Schmidt-Ruppin strain of Rous sarcoma virus. The cells were made permeable to nucleoside triphosphates by treatment with a hypotonic buffer containing 10 mM Tris Cl, 4 mM MgCl2, 1 mM EDTA, and 6 mM 2-...

    journal_title：Cancer research

    pub_type： 杂志文章

    doi：

    authors： Seki S,Oda T

    更新日期：1977-01-01 00:00:00

  • Antagonistic effect of glucocorticoids on retinoic acid induced growth inhibition and morphological alterations of a human cell line.

    abstract：:When the human cell line NHIK 3025 was exposed to retinoic acid (1 nM; 10 microM), the cell cycle time was prolonged. Experiments using cells synchronized by mitotic selection showed that the retinoic acid induced growth delay was barely seen within the first cell cycle after exposure to 10 microM retinoic acid, where...

    journal_title：Cancer research

    pub_type： 杂志文章

    doi：

    authors： Bakke O

    更新日期：1986-03-01 00:00:00

  • Total serum cholesterol and triglycerides and risk of breast cancer: a prospective study of 24,329 Norwegian women.

    abstract：:The association between total serum cholesterol and triglycerides and the incidence rate of breast cancer has been examined in 242 incident cases of breast cancer that developed among 24,329 Norwegian women during 11-14 years of follow-up. At the time of lipid measurement they were between 35 and 51 years of age. Ther...

    journal_title：Cancer research

    pub_type： 杂志文章

    doi：

    authors： Vatten LJ,Foss OP

    更新日期：1990-04-15 00:00:00

  • Patient-derived tumor xenografts: transforming clinical samples into mouse models.

    abstract：:Tumor graft models (also known as patient-derived xenografts or PDX) are based on the transfer of primary tumors directly from the patient into an immunodeficient mouse. Because PDX mice are derived from human tumors, they offer a tool for developing anticancer therapies and personalized medicine for patients with can...

    journal_title：Cancer research

    pub_type： 杂志文章,评审

    doi：10.1158/0008-5472.CAN-13-1069

    authors： Siolas D,Hannon GJ

    更新日期：2013-09-01 00:00:00

  • Activity of a novel 4-quinolinecarboxylic acid, NSC 368390 [6-fluoro-2-(2'-fluoro-1,1'-biphenyl-4-yl)-3-methyl-4-quinolinecarb oxylic acid sodium salt], against experimental tumors.

    abstract：:A novel, substituted 4-quinolinecarboxylic acid (NSC 339768) demonstrated antitumor activity against L1210 leukemia and B16 melanoma in the National Cancer Institute's Developmental Therapeutics Program. An extensive analogue synthesis program was initiated; over 200 derivatives were synthesized and tested for antican...

    journal_title：Cancer research

    pub_type： 杂志文章

    doi：

    authors： Dexter DL,Hesson DP,Ardecky RJ,Rao GV,Tippett DL,Dusak BA,Paull KD,Plowman J,DeLarco BM,Narayanan VL

    更新日期：1985-11-01 00:00:00