Isocitrate dehydrogenase 1-snail axis dysfunction significantly correlates with breast cancer prognosis and regulates cell invasion ability.

Abstract:

BACKGROUND:The isocitrate dehydrogenase (IDH) gene family expresses key functional metabolic enzymes in the Krebs cycle and mediates the epigenetic reprogramming, which serves as an important biomarker of breast cancer. However, the expression levels of the IDH protein and their biological function in human breast cancer remain largely unknown. METHODS:In this study, the clinical impact of IDH1 expression on the progression and prognosis of breast cancer was evaluated using immunohistochemistry assay (IHC) of the corresponding tumor-adjacent normal, ductal carcinoma in situ (DCIS), and invasive ductal carcinoma (IDC) tissues from 309 patients with breast ductal carcinoma. The relationship between microRNA (miRNA) and IDH1 were examined by a bioinformatics approach, western blot and reporter assay. The biological functions of IDH1 were examined in breast cancer cells with IDH1 knockdown, including proliferation, migration and invasion. RESULTS:The present findings revealed that the mRNA and protein expression levels of IDH1 were both significantly lower in breast cancer tissues than in adjacent normal tissues. A low expression level of IDH1 in breast cancer significantly correlated with advanced stage (p = 0.012), lymph node metastasis (p = 0.018), and poor disease-specific survival (DSS) (adjusted hazard ratio (AHR), 1.57, 95% confidence interval (CI), 1.08-2.30; p = 0.02). Furthermore, oncogenic miR-32 and miR-92b were identified to suppress IDH1 expression, leading to the inhibition of cell migration and invasion. We further explored whether reduced expression of IDH1 significantly increases snail expression by activating HIFα (hypoxia-inducible factor-1 alpha) and NFκB (nuclear factor kappa B) signaling. Multivariate Cox regression analysis revealed that the combination of low IDH1 and high snail expression could be an independent risk factor for shorter DSS (AHR, 2.34; 95% CI, 1.32-4.16; p = 0.004) and shorter disease-free survival (AHR, 2.50; 95% CI, 1.39-4.50; p = 0.002) in patients with breast cancer. CONCLUSION:Our findings revealed that a IDH1low/Snailhigh molecular signature could serve as an independent biomarker for poor prognosis in breast cancer.

journal_name

Breast Cancer Res

authors

Liu WS,Chan SH,Chang HT,Li GC,Tu YT,Tseng HH,Fu TY,Chang HY,Liou HH,Ger LP,Tsai KW

doi

10.1186/s13058-018-0953-7

subject

Has Abstract

pub_date

2018-04-16 00:00:00

pages

25

issue

1

eissn

1465-5411

issn

1465-542X

pii

10.1186/s13058-018-0953-7

journal_volume

20

pub_type

杂志文章
  • 17-allyamino-17-demethoxygeldanamycin treatment results in a magnetic resonance spectroscopy-detectable elevation in choline-containing metabolites associated with increased expression of choline transporter SLC44A1 and phospholipase A2.

    abstract:INTRODUCTION:17-allyamino-17-demethoxygeldanamycin (17-AAG), a small molecule inhibitor of Hsp90, is currently in clinical trials in breast cancer. However, 17-AAG treatment often results in inhibition of tumor growth rather than shrinkage, making detection of response a challenge. Magnetic resonance spectroscopy (MRS)...

    journal_title:Breast cancer research : BCR

    pub_type: 杂志文章

    doi:10.1186/bcr2729

    authors: Brandes AH,Ward CS,Ronen SM

    更新日期:2010-01-01 00:00:00

  • Progesterone receptors--animal models and cell signalling in breast cancer. Diverse activation pathways for the progesterone receptor: possible implications for breast biology and cancer.

    abstract::Progesterone and estradiol, and their nuclear receptors, play essential roles in the physiology of the reproductive tract, the mammary gland and the nervous system. Estrogens have traditionally been considered associated with an increased risk of breast cancer. There is, however, compelling evidence that progesterone ...

    journal_title:Breast cancer research : BCR

    pub_type: 杂志文章,评审

    doi:10.1186/bcr539

    authors: Lanari C,Molinolo AA

    更新日期:2002-01-01 00:00:00

  • Association of phosphatase and tensin homolog low and phosphatidylinositol 3-kinase catalytic subunit alpha gene mutations on outcome in human epidermal growth factor receptor 2-positive metastatic breast cancer patients treated with first-line lapatinib

    abstract:INTRODUCTION:Phosphatidylinositol 3-kinase (PI3K) pathway deregulation (that is PIK3CA mutations and/or phosphatase and tensin homolog (PTEN) loss) has been shown to enhance breast cancer cell survival and confer resistance to chemotherapeutic agents. We studied the prognostic and predictive value of PIK3CA mutations a...

    journal_title:Breast cancer research : BCR

    pub_type: 杂志文章

    doi:10.1186/s13058-014-0405-y

    authors: Xu B,Guan Z,Shen Z,Tong Z,Jiang Z,Yang J,DeSilvio M,Russo M,Leigh M,Ellis C

    更新日期:2014-07-24 00:00:00

  • Nongenomic oestrogen signalling in oestrogen receptor negative breast cancer cells: a role for the angiotensin II receptor AT1.

    abstract:INTRODUCTION:Oestrogens can mediate some of their cell survival properties through a nongenomic mechanism that involves the mitogen-activated protein kinase (MAPK) pathway. The mechanism of this rapid signalling and its dependence on a membrane bound oestrogen receptor (ER), however, remains controversial. The role of ...

    journal_title:Breast cancer research : BCR

    pub_type: 杂志文章

    doi:10.1186/bcr1509

    authors: Lim KT,Cosgrave N,Hill AD,Young LS

    更新日期:2006-01-01 00:00:00

  • Sunitinib inhibits lymphatic endothelial cell functions and lymph node metastasis in a breast cancer model through inhibition of vascular endothelial growth factor receptor 3.

    abstract:INTRODUCTION:Metastasis is a common event and the main cause of death in cancer patients. Lymphangiogenesis refers to the formation of new lymphatic vessels and is thought to be involved in the development of metastasis. Sunitinib is a multi-kinase inhibitor that blocks receptor tyrosine kinase activity, including that...

    journal_title:Breast cancer research : BCR

    pub_type: 杂志文章

    doi:10.1186/bcr2903

    authors: Kodera Y,Katanasaka Y,Kitamura Y,Tsuda H,Nishio K,Tamura T,Koizumi F

    更新日期:2011-06-21 00:00:00

  • The effect of psychosocial factors on breast cancer outcome: a systematic review.

    abstract:INTRODUCTION:We sought to review the available evidence regarding the effect of psychosocial factors on the survival of breast cancer patients. METHODS:We systematically searched the PubMed and PsycINFO databases to identify relevant studies. RESULTS:We identified 31 studies examining the association of various psych...

    journal_title:Breast cancer research : BCR

    pub_type: 杂志文章,meta分析

    doi:10.1186/bcr1744

    authors: Falagas ME,Zarkadoulia EA,Ioannidou EN,Peppas G,Christodoulou C,Rafailidis PI

    更新日期:2007-01-01 00:00:00

  • HER-2 positive breast cancer: decreasing proportion but stable incidence in Finnish population from 1982 to 2005.

    abstract:INTRODUCTION:Classification of breast cancers according to the HER-2 oncogene status is of central importance in the selection of post-surgical therapies. A decrease in the proportion of HER-2-positive breast cancer has been suspected, but no data on the incidence trends at population level have been reported. METHODS...

    journal_title:Breast cancer research : BCR

    pub_type: 杂志文章

    doi:10.1186/bcr2322

    authors: Köninki K,Tanner M,Auvinen A,Isola J

    更新日期:2009-01-01 00:00:00

  • Prognostic significance of tumor-infiltrating CD8+ and FOXP3+ lymphocytes in residual tumors and alterations in these parameters after neoadjuvant chemotherapy in triple-negative breast cancer: a retrospective multicenter study.

    abstract:INTRODUCTION:The status of tumor-infiltrating lymphocytes (TILs) has been recently proposed to predict clinical outcome of patients with breast cancer. We therefore studied the prognostic significance of CD8(+) TILs and FOXP3(+) TILs in residual tumors after neoadjuvant chemotherapy (NAC) and the alterations in these p...

    journal_title:Breast cancer research : BCR

    pub_type: 杂志文章,多中心研究

    doi:10.1186/s13058-015-0632-x

    authors: Miyashita M,Sasano H,Tamaki K,Hirakawa H,Takahashi Y,Nakagawa S,Watanabe G,Tada H,Suzuki A,Ohuchi N,Ishida T

    更新日期:2015-09-04 00:00:00

  • RAD51C deletion screening identifies a recurrent gross deletion in breast cancer and ovarian cancer families.

    abstract::RAD51C is an integral part of the DNA double-strand repair through homologous recombination, and monoallelic mutations were found in ~1.3% of BRCA1/2-negative breast cancer (BC) and/or ovarian cancer (OC) families. Several studies confirmed the occurrence of RAD51C mutations predominantly in BC and/or OC families, alt...

    journal_title:Breast cancer research : BCR

    pub_type: 信件

    doi:10.1186/bcr3589

    authors: Schnurbein G,Hauke J,Wappenschmidt B,Weber-Lassalle N,Engert S,Hellebrand H,Garbes L,Becker A,Neidhardt G,Rhiem K,Meindl A,Schmutzler RK,Hahnen E

    更新日期:2013-12-20 00:00:00

  • Immortalized, pre-malignant epithelial cell populations contain long-lived, label-retaining cells that asymmetrically divide and retain their template DNA.

    abstract:INTRODUCTION:During selective segregation of DNA, a cell asymmetrically divides and retains its template DNA. Asymmetric division yields daughter cells whose genome reflects that of the parents', simultaneously protecting the parental cell from genetic errors that may occur during DNA replication. We hypothesized that ...

    journal_title:Breast cancer research : BCR

    pub_type: 杂志文章

    doi:10.1186/bcr2754

    authors: Bussard KM,Boulanger CA,Kittrell FS,Behbod F,Medina D,Smith GH

    更新日期:2010-01-01 00:00:00

  • Cooperative signaling between Wnt1 and integrin-linked kinase induces accelerated breast tumor development.

    abstract:INTRODUCTION:Breast cancer is genetically and clinically a heterogeneous disease. However, the exact contribution of different cell types and oncogenic mutations to this heterogeneity are not well understood. Recently, we discovered an interaction between Wnt and integrin-linked kinase (ILK) within the signaling cascad...

    journal_title:Breast cancer research : BCR

    pub_type: 杂志文章

    doi:10.1186/bcr2592

    authors: Oloumi A,Maidan M,Lock FE,Tearle H,McKinney S,Muller WJ,Aparicio SA,Dedhar S

    更新日期:2010-01-01 00:00:00

  • CD24(+) cells fuel rapid tumor growth and display high metastatic capacity.

    abstract:INTRODUCTION:Breast tumors are comprised of distinct cancer cell populations which differ in their tumorigenic and metastatic capacity. Characterization of cell surface markers enables investigators to distinguish between cancer stem cells and their counterparts. CD24 is a well-known cell surface marker for mammary epi...

    journal_title:Breast cancer research : BCR

    pub_type: 杂志文章

    doi:10.1186/s13058-015-0589-9

    authors: Rostoker R,Abelson S,Genkin I,Ben-Shmuel S,Sachidanandam R,Scheinman EJ,Bitton-Worms K,Orr ZS,Caspi A,Tzukerman M,LeRoith D

    更新日期:2015-06-04 00:00:00

  • NHERF1: molecular brake on the PI3K pathway in breast cancer.

    abstract::The adaptor protein NHERF1/EBP50 (Na/H exchanger regulatory factor 1/ezrin-radixin-moesin-binding phosphoprotein 50) emerged recently as an important player in breast cancer progression. Consisting of two tandem PDZ domains linked to a carboxyl-terminal ezrin-binding region, NHERF1 assembles macromolecular complexes a...

    journal_title:Breast cancer research : BCR

    pub_type: 评论,社论

    doi:10.1186/bcr1992

    authors: Georgescu MM

    更新日期:2008-01-01 00:00:00

  • Common ataxia telangiectasia mutated haplotypes and risk of breast cancer: a nested case-control study.

    abstract:INTRODUCTION:The ataxia telangiectasia mutated (ATM) gene is a tumor suppressor gene with functions in cell cycle arrest, apoptosis, and repair of DNA double-strand breaks. Based on family studies, women heterozygous for mutations in the ATM gene are reported to have a fourfold to fivefold increased risk of breast canc...

    journal_title:Breast cancer research : BCR

    pub_type: 杂志文章

    doi:10.1186/bcr809

    authors: Tamimi RM,Hankinson SE,Spiegelman D,Kraft P,Colditz GA,Hunter DJ

    更新日期:2004-01-01 00:00:00

  • Breast cancer stem cells: implications for therapy of breast cancer.

    abstract::The concept of cancer stem cells responsible for tumour origin, maintenance, and resistance to treatment has gained prominence in the field of breast cancer research. The therapeutic targeting of these cells has the potential to eliminate residual disease and may become an important component of a multimodality treatm...

    journal_title:Breast cancer research : BCR

    pub_type: 杂志文章,评审

    doi:10.1186/bcr2111

    authors: Morrison BJ,Schmidt CW,Lakhani SR,Reynolds BA,Lopez JA

    更新日期:2008-01-01 00:00:00

  • Upregulation of EGFR signaling is correlated with tumor stroma remodeling and tumor recurrence in FGFR1-driven breast cancer.

    abstract:INTRODUCTION:Despite advances in early detection and adjuvant targeted therapies, breast cancer is still the second most common cause of cancer mortality among women. Tumor recurrence is one of the major contributors to breast cancer mortality. However, the mechanisms underlying this process are not completely understo...

    journal_title:Breast cancer research : BCR

    pub_type: 杂志文章

    doi:10.1186/s13058-015-0649-1

    authors: Holdman XB,Welte T,Rajapakshe K,Pond A,Coarfa C,Mo Q,Huang S,Hilsenbeck SG,Edwards DP,Zhang X,Rosen JM

    更新日期:2015-11-18 00:00:00

  • A deep learning image-based intrinsic molecular subtype classifier of breast tumors reveals tumor heterogeneity that may affect survival.

    abstract:BACKGROUND:Breast cancer intrinsic molecular subtype (IMS) as classified by the expression-based PAM50 assay is considered a strong prognostic feature, even when controlled for by standard clinicopathological features such as age, grade, and nodal status, yet the molecular testing required to elucidate these subtypes i...

    journal_title:Breast cancer research : BCR

    pub_type: 杂志文章

    doi:10.1186/s13058-020-1248-3

    authors: Jaber MI,Song B,Taylor C,Vaske CJ,Benz SC,Rabizadeh S,Soon-Shiong P,Szeto CW

    更新日期:2020-01-28 00:00:00

  • Measuring proliferation in breast cancer: practicalities and applications.

    abstract::Various methods are available for the measurement of proliferation rates in tumours, including mitotic counts, estimation of the fraction of cells in S-phase of the cell cycle and immunohistochemistry of proliferation-associated antigens. The evidence, advantages and disadvantages for each of these methods along with ...

    journal_title:Breast cancer research : BCR

    pub_type: 杂志文章,评审

    doi:10.1186/bcr1618

    authors: Beresford MJ,Wilson GD,Makris A

    更新日期:2006-01-01 00:00:00

  • A whole slide image-based machine learning approach to predict ductal carcinoma in situ (DCIS) recurrence risk.

    abstract:BACKGROUND:Breast ductal carcinoma in situ (DCIS) represent approximately 20% of screen-detected breast cancers. The overall risk for DCIS patients treated with breast-conserving surgery stems almost exclusively from local recurrence. Although a mastectomy or adjuvant radiation can reduce recurrence risk, there are sig...

    journal_title:Breast cancer research : BCR

    pub_type: 杂志文章

    doi:10.1186/s13058-019-1165-5

    authors: Klimov S,Miligy IM,Gertych A,Jiang Y,Toss MS,Rida P,Ellis IO,Green A,Krishnamurti U,Rakha EA,Aneja R

    更新日期:2019-07-29 00:00:00

  • Phosphoinositide 3-kinase targeting by the beta galactoside binding protein cytokine negates akt gene expression and leads aggressive breast cancer cells to apoptotic death.

    abstract:INTRODUCTION:Phosphoinositide 3-kinase (PI3K)-activated signalling has a critical role in the evolution of aggressive tumourigenesis and is therefore a prime target for anticancer therapy. Previously we have shown that the beta galactoside binding protein (betaGBP) cytokine, an antiproliferative molecule, induces funct...

    journal_title:Breast cancer research : BCR

    pub_type: 杂志文章

    doi:10.1186/bcr2217

    authors: Wells V,Mallucci L

    更新日期:2009-01-01 00:00:00

  • Metastatic breast cancer cells overexpress and secrete miR-218 to regulate type I collagen deposition by osteoblasts.

    abstract:BACKGROUND:Bone is one of the most frequent metastatic sites of advanced breast cancer. Current therapeutic agents aim to inhibit osteoclast-mediated bone resorption but only have palliative effects. During normal bone remodeling, the balance between bone resorption and osteoblast-mediated bone formation is essential f...

    journal_title:Breast cancer research : BCR

    pub_type: 杂志文章

    doi:10.1186/s13058-018-1059-y

    authors: Liu X,Cao M,Palomares M,Wu X,Li A,Yan W,Fong MY,Chan WC,Wang SE

    更新日期:2018-10-22 00:00:00

  • Impact of intercensal population projections and error of closure on breast cancer surveillance: examples from 10 California counties.

    abstract:INTRODUCTION:In 2001, data from the California Cancer Registry suggested that breast cancer incidence rates among non-Hispanic white (nHW) women in Marin County, California, had increased almost 60% between 1991 and 1999. This analysis examines the extent to which these and other breast cancer incidence trends could ha...

    journal_title:Breast cancer research : BCR

    pub_type: 杂志文章

    doi:10.1186/bcr1266

    authors: Phipps AI,Clarke CA,Ereman RR

    更新日期:2005-01-01 00:00:00

  • The estrogen receptor influences microtubule-associated protein tau (MAPT) expression and the selective estrogen receptor inhibitor fulvestrant downregulates MAPT and increases the sensitivity to taxane in breast cancer cells.

    abstract:INTRODUCTION:Microtubule-associated protein tau (MAPT) inhibits the function of taxanes and high expression of MAPT decreases the sensitivity to taxanes. The relationship between estrogen receptor (ER) and MAPT in breast cancer is unclear. In this study, we examined the correlation of MAPT expression with the sensitivi...

    journal_title:Breast cancer research : BCR

    pub_type: 杂志文章

    doi:10.1186/bcr2598

    authors: Ikeda H,Taira N,Hara F,Fujita T,Yamamoto H,Soh J,Toyooka S,Nogami T,Shien T,Doihara H,Miyoshi S

    更新日期:2010-01-01 00:00:00

  • Additive growth inhibitory effects of ibandronate and antiestrogens in estrogen receptor-positive breast cancer cell lines.

    abstract:INTRODUCTION:Bisphosphonates are inhibitors of osteoclast-mediated tumor-stimulated osteolysis, and they have become standard therapy for the management of bone metastases from breast cancer. These drugs can also directly induce growth inhibition and apoptosis of osteotropic cancer cells, including estrogen receptor-po...

    journal_title:Breast cancer research : BCR

    pub_type: 杂志文章

    doi:10.1186/bcr1363

    authors: Journe F,Chaboteaux C,Magne N,Duvillier H,Laurent G,Body JJ

    更新日期:2006-01-01 00:00:00

  • Update on HER-2 as a target for cancer therapy: intracellular signaling pathways of ErbB2/HER-2 and family members.

    abstract::ErbB (also termed HER) receptors are expressed in various tissues of epithelial, mesenchymal and neuronal origin, in which they are involved in the control of diverse biological processes such as proliferation, differentiation, migration and apoptosis. Furthermore, their deregulated expression has been implicated in m...

    journal_title:Breast cancer research : BCR

    pub_type: 杂志文章,评审

    doi:10.1186/bcr327

    authors: Olayioye MA

    更新日期:2001-01-01 00:00:00

  • Common genetic variation and novel loci associated with volumetric mammographic density.

    abstract:BACKGROUND:Mammographic density (MD) is a strong and heritable intermediate phenotype of breast cancer, but much of its genetic variation remains unexplained. METHODS:We conducted a genetic association study of volumetric MD in a Swedish mammography screening cohort (n = 9498) to identify novel MD loci. Associations w...

    journal_title:Breast cancer research : BCR

    pub_type: 杂志文章

    doi:10.1186/s13058-018-0954-6

    authors: Brand JS,Humphreys K,Li J,Karlsson R,Hall P,Czene K

    更新日期:2018-04-17 00:00:00

  • Dynamic regulation of CD24 and the invasive, CD44posCD24neg phenotype in breast cancer cell lines.

    abstract:INTRODUCTION:The invasive, mesenchymal phenotype of CD44posCD24neg breast cancer cells has made them a promising target for eliminating the metastatic capacity of primary tumors. It has been previously demonstrated that CD44neg/lowCD24pos breast cancer cells lack the ability to give rise to their invasive CD44posCD24ne...

    journal_title:Breast cancer research : BCR

    pub_type: 杂志文章

    doi:10.1186/bcr2449

    authors: Meyer MJ,Fleming JM,Ali MA,Pesesky MW,Ginsburg E,Vonderhaar BK

    更新日期:2009-01-01 00:00:00

  • A migrant study of pubertal timing and tempo in British-Bangladeshi girls at varying risk for breast cancer.

    abstract:INTRODUCTION:Earlier menarche is related to subsequent breast cancer risk, yet international differences in the age and tempo of other pubertal milestones and their relationships with body mass index (BMI) are not firmly established in populations at differing risk for breast cancer. We compared age and tempo of adrena...

    journal_title:Breast cancer research : BCR

    pub_type: 杂志文章

    doi:10.1186/s13058-014-0469-8

    authors: Houghton LC,Cooper GD,Bentley GR,Booth M,Chowdhury OA,Troisi R,Ziegler RG,Hoover RN,Katki HA

    更新日期:2014-11-15 00:00:00

  • Pregnancy-induced changes in cell-fate in the mammary gland.

    abstract::The protective effect of an early full-term pregnancy is a well established phenomenon; in contrast, the molecular and cell-specific mechanisms that govern parity-specific changes in the mammary gland have not been well described. Recent studies signify a dramatic advance in our understanding of this phenomenon, and i...

    journal_title:Breast cancer research : BCR

    pub_type: 杂志文章

    doi:10.1186/bcr603

    authors: Ginger MR,Rosen JM

    更新日期:2003-01-01 00:00:00

  • Plasma levels of leptin and mammographic density among postmenopausal women: a cross-sectional study.

    abstract:INTRODUCTION:Obesity has been linked to increased risk of breast cancer in postmenopausal women. Increased peripheral production of estrogens has been regarded as the main cause for this association, but other features of increased body fat mass may also play a part. Leptin is a protein produced mainly by adipose tissu...

    journal_title:Breast cancer research : BCR

    pub_type: 杂志文章

    doi:10.1186/bcr1603

    authors: Stuedal A,Ursin G,Veierød MB,Bremnes Y,Reseland JE,Drevon CA,Gram IT

    更新日期:2006-01-01 00:00:00