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Figure Legend Schematic illustration of the major molecular pathways and transcription factors associated with EMT program in EEC. Several microRNAs regulate the EMT inducing signaling pathways and the core EMT regulators. Sharp arrows denote activation and blunt arrows indicate inhibition. Dotted lines indicate the presence of intermediate signaling molecules (not shown). End points of the EMT program are boxed (see text for details) 13x9mm (600 x 600 DPI)
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Legend to figure Schematic illustration of the major molecular pathways and transcription factors associated with EMT program in EEC. Several microRNAs regulate the EMT inducing signaling pathways and the core EMT regulators. Sharp arrows denote activation and blunt arrows indicate inhibition. Dotted lines indicate the presence of intermediate signaling molecules (not shown). End points of the EMT program are boxed (see text for details).
267x189mm (72 x 72 DPI)
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Table: Summary of molecular events associated with EMT in progression, invasion and metastasis of EEC Factors
Steroid hormones and their receptors
ER-A loss in EC is associated with increased EMT, vascular invasion, deep myometrial invasion. ER-A negative EC associated with increased expression of SNAIL, reduced E-cadherin expression and tumor progression. Absence of ER-A leads to an increased incidence of in situ and invasive carcinoma. NPM1 overexpression may play a role in the effects of estrogen on the malignant progression of EEC via ER-A signaling. Absent or reduced ER-A during EC progression may be due to loss of FOXA1 function.
ER-B is important in progression of myometrial invasion.
Loss of PR is associated with increased CD44 and decreased Ecadherin expression. Progression of EEC characterized by loss of PR, increased EMT, loss of immunosuppression , more invasive phenotype.
Loss of PR particularly in stroma indicates invasive characteristic of tumor; relative PR-B overexpression related to metastatic potential. PR-B status controls EMT. PR-B activation inhibits cell growth and invasiveness via suppression of expression of MMPs and Ets-1. EMT a late event in endometrial carcinogenesis, linked to loss of hormone receptors.
Cell signaling pathways PI3K/Akt/mTOR EGFR acting upstream of PI3K/Akt plays initiating role to stimulate signaling EMT via SNAIL upregulation and E-cadherin downregulation. EGFR shows negative correlation with epithelial markers and a positive correlation with mesenchymal markers in EC cells transfected with EGFR. IR/IGF-1R induce EH and promote EEC cell growth through activation of PI3K/Akt/mTOR signaling. Anti-invasive and anti-metastatic effect of metformin in EC cells associated with MMP-2/9 and Akt, NFκB and ERK1/2 signaling. Transcriptional changes in the PI3K pathway are early events in the invasive step to grade I EEC.
Clinical material/model* Tumor samples FIGO stageI/II and III/IV (n=76/155/286/111) Primary tumors (n=87) and metastases (n=26) of EEC Pten +/- ERα-/- mouse model Pten deleted Hec1A cells Tumor samples FIGO stages I, II, III and IV (n=56) Tissue samples from AH and EC (n=86); Ishikawa, RL95-2, Hec IB and AN3CA cell lines Tumor samples FIGO stages I, II, III and IV (n=214) Ishikawa PRAB-36 cells
Reference Wik et al. 2013
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Zhou et al. 2014
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Hanekamp et al. 2003
Non-progressive (n=9) and progressive (n=9) primary tumor tissues, Ishikawa cells Grade I and II FFPE tumor samples (n=15) Ishikawa cell line
Van der Horst et al. 2012
Tissue from CAH, primary EEC and metastatic lesions from EECs (n=729)
FFPE samples of CAH and Grade 1 EEC (n=44) ECC-1 cells
McCampbell et al. 2006 Tan et al. 2011
Tissue from CAH, primary EEC and metastatic lesions from EECs (n=729)
Berg et al. 2015
Yang et al. 2014
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Ras/Raf/MEK/MAPK/ ERK signaling
Loss of PTEN expression is an early event in endometrial tumorigenesis. Loss of Cdh1 promotes aggressive EC phenotypes when cells are initiated by ablation of Pten. Pten+/- ER-/-mice show a higher incidence of in situ and invasive carcinoma. Progression of EC is associated with PTEN mutation, estrogen treatment induces more severe endometrial tumorigenesis. Low ER-A associated with markers for EMT, Stathmin (a marker associated with PTEN loss) and a high PI3K activation signature Lkb1 inactivation promotes development of invasive EC. Concomitant loss of pten and lkb1 leads to rapid development of advanced EEC with 100% penetrance. Raf-1/MAPK mediates EGF action; stimulates EpCAM cleavage and internalization of EpICD into the nucleus to activate mesenchymal cadherins accompanied by loss of E-cadherin and upregulation of SNAIL EGFR via Akt and ERK1/2 pathways regulates expression of SNAIL in Ishikawa cells. MAPK/ERK pathway is involved in the progression and invasion of EEC mediated by EMT. Up-regulated expression of kinase suppressor of RAS1 is responsible for endometrial carcinogenesis as well as anchorage-independent cell growth. GPR30 signaling via the MEK/MAPK/ERK pathway promotes cell proliferation and the invasion potential of EC cells through its action on MMP-2, MMP-9. Conditional Pten ablation and K-ras mutation significantly accelerates development of EC. PI3K and KRAS signaling activation suggested as early events in the development from CAH to EEC. Conditional ablation and activation of B-catenin leads to aberrant epithelial structures and EH formation.
LEF1, cyclinD1 and MMP-7 play a role in endometrial gland formation and carcinogenesis.
FFPE endometrial tissue of PE, SH, CAH and EEC (n=87) Cdhd/d, Ptend/d, Cdhd/dPtend/d mouse models
Sarmadi et al. 2009
Pten+/- ER-/- mouse model
Joshi et al. 2012
PRcre/+ Ptenf/f and Ptend/d mouse models
Kim et al. 2013
Tumor samples FIGO stageI/II and III/IV (n=76/155/286/111) Sprr2f-Cre transgenic mouse model Ptenloxp/loxpLkb1loxp/loxp mouse model
Wik et al. 2013
Normal and malignant endometrial cells; EC samples
Hsu et al. 2014
FFPE primary tumor samples (n=17), 2 Ishikawa cell lines Tumor samples (n=42) Stage I (IA, IB and IC) Tumor samples (Grades 1,2and 3, stages I to IV) (n=24/26); Ishikawa 3-H-12, KLE, RL-95 and HEC-1A cell lines Tumor samples (n=50), RL95-2 and KLE cells
Hipp et al. 2009
Double mutant mouse model PRcre/+Ptenf/fK-rasG12D; Ptend/dK-rasG12D Tissue from CAH, primary EEC and metastatic lesions from EECs (n=729) K5Cre;Catnb(ex3)fl/+ mouse model, Ishikawa and ECC-1 cell lines. UE2AA- a mouse derived endometrial cell line. Human specimens of eutopic endometrium (n=3), CAH (n=28), EACs(G1& G3, n=41) Lef1 knockout mice and wild type controls; human tumor samples (n=99)
Kim et al. 2010b
Lindberg et al. 2013
Contreras et al. 2010 Cheng et al. 2014
Montserrat et al. 2011
Llobet et al. 2011
He et al. 2009
Berg et al. 2015
Villacorte et al. 2013
Shelton et al. 2012
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B-catenin expression associated with loss of E-cadherin is involved in acquisition of aggressive biological behavior, especially in high grade ECs. Inhibition of Wnt signaling by Dickkopf-3 is accompanied by decreased proliferation, reduced anchorage independent growth and decreased invasiveness. Wnt/B-catenin and PTEN pathways have a synergistic effect on EC onset, progression and acquisition of a more aggressive malignant behavior. TGFB1 plays important role in the initial steps of EC invasion by promoting EMT leading to acquisition of an invasive phenotype. Abrogation of TGFBR signaling induces apoptosis and reduces invasive and metastatic potential by reversal of autocrine TGFBinduced EMT. Progesterone inhibits basal and TGFB1 induced cancer cell viability and invasion accompanied by increased E-cadherin and decreased vimentin expression. TGFB upregulates prostate apoptosis response-4expression with simultaneous induction of EMT. Emmprin knockdown leads to inhibition of cell proliferation, migration and invasion through TGFB, EGF, NFKB, VEGF, MMP-2, MMP-9 resuting in increased levels of E-cadherin and reduced levels of vimentin and SNAIL. Expression of signaling elements of Hedgehog pathway increase stepwisely in EH and EC; activation of this pathway is involved in malignant transformation of EC.
Over expression of Gli1 proposed as an early event in endometrial tumorigenesis. Gli induces SNAIL which suppresses E-cadherin and displaces B-catenin from adherens junctions.
Upregulation of NFKB activity observed in human EC cells expressing phospho-Akt is responsible for the increase of COX-2 gene expression closely associated with parameters of tumor aggressiveness. COX-2 and NFKB signaling mediates the progression of hyperplasia to cancer.
Blockade of NFKB activity by Sunitinib reduces cell viability, proliferation, clongenicity and induces apoptotic cell death.
Tumor samples (FIGO stage I to IV) (n=73)
Shih et al. 2004
Tumor samples (n=27) Stage I/II and II/IV;T-HESC, ECC-1, HEC-iA and RL95-2 cell lines; mouse xenograft model PgrCre/+, Apc15lox/+, Ptenex5lox/- mouse models
Dellinger et al. 2012
Tumor samples (n=51); HEC1A and RL95-2 cell lines HEC1-A cells
Muinelo-Romay et al. 2011 Lei et al. 2009
Ishikawa, HEC-1B and RL95-2 cell lines
Bokhari et al. 2014
KLE and HEC1A cell lines
Chaudhry et al. 2014
Endometrial tissue normal, hyperplasia, adenocarcinoma and carcinosarcoma (n=164); HEC-50B and KLE cells
Nakamura et al. 2012
Tissue from EH (simple, complex, atypical) and EC (Stage I to IV) (n=112); Ishikawa, HEC1A/B, HHUA, KLE and RL95-2 cell lines FFPE samples EC (n=80; stages I-IV), Normal endometrium (PE, SE, interval, n=15), EH (simple and complex, n=14), CAH (n=37); Hec-1A, Hec-1B and RL952 cell lines Hec1-A, RL 95-2 and Ishikawa cell lines
Feng et al. 2007
Tissue samples of benign endometrial polyps, EH, endometrial intraepithelial neoplasia and EEC Ishikawa 3-H-12, RL-95 and Hec-1A cell lines
Faloppa et al. 2014
Van der Zee et al. 2013
Liao et al. 2009
St-Germain et al. 2004
Sorolla et al. 2012
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NFKB activation is a novel target of oncogenic KRAS signals in endometrial carcinogenesis. Receptor activator of NFKB (RANK) and its ligand promote EC cell proliferation, migration and invasion via the MAPK pathway.
Hypoxia signaling pathway
Leptin potently induces invasion of EC cells in matrigel invasion assay which is effectively blocked by pharmacological inhibitors of JAK/STAT and PI3K. Functional activation of COX-2 in EC cells is induced by leptin through JAK2/STAT3, MAPK/ERK and PI3K/Akt pathways.
Leptin promotes EC growth and invasiveness by activating STAT3 and ERK1/2 signaling pathways which is effectively blocked by inhibitors of STAT3 (AG490) and ERK1/2 (PD98059). A critical role for HIF-1a/TWIST/E-cadherin system has been suggested in malignant progression and acquisition of metastatic phenotype in EEC. HIF-1pathway and its target genes, particularly DEC2 (SHARP1) play an important role in endometrial carcinogenesis and tumor phenotype development. SHARP1 has a tumor suppressive function during EC progression especially in the regulation of angiogenesis. Higher HIF-1A expression has been suggested to be associated with the higher risk of recurrence. TrkB and BDNF are involved in EC tumorigenesis and metastasis. TWIST expression is modulated by TrkB, and is essential for TrkB induced EMT like transformation and anoikis resistance. TrkB-STAT3-miR204-5p circuitry regulates clonogenic growth, migration and invasion of EC cells. Reduced miR-204-5p expression correlates with tumor stage and lymph node metastasis. BDNF demonstrates a principal role coordinating ETV5-mediated EMT in EC. Impairment of BDNF/TrkB/ERK axis in EC cells reversed the aggressive and invasive phenotype promoted by upregulation of ETV5 at the invasive front. ETV5-related proteomic approach reinforces role of this transcription factor in regulation of the migratory and invasive tumor behavior
SHARP1 regulates Notch/EMT pathway in EC. Positive correlation
In vitro carcinogenesis model with human endometrial epithelial cells Endometrial tissue normal, EAH and EC (n=120). Ishikawa, KLE, AN3CA, RL 952 and HEC-1B cell lines Ishikawa and ECC1 cell lines
Mizumoto et al. 2011
Ishikawa, ECC-1, Hec-1A, Hec-1B, RL952 and AN3CA cell lines
Gao et al. 2009
Ishikawa cell line
Liu et al. 2011
Tissue samples from AH and EEC (n=152)
Feng et al. 2013
Tissue samples from CAH and EC (n=86); Ishikawa, HEC-1, SNG-II and SNG-M cell lines Tumor samples (n=110); Ishikawa and RL95-2 cell lines Tumor samples, stages IA, IB, II, IIIA, IIIC and IV (n=92) Tissue samples from AH and EC (n=130); Ishikawa, RL95-2, HEC-1B, KLE, AN3CA and SPEC2 cell lines Tumor samples (n=110); Ishikawa and HEC-1B cell lines; mouse xenografts
Yunokawa et al. 2007
Wang et al. 2015
Sharma et al. 2006
Liao et al. 2014
Sadlecki et al. 2014
Bao et al. 2013a
Bao et al. 2013b
Tumor samples (EEC stage IB, n= 13); HEC1A and HEC1A-ETV5 cell lines; in vivo mouse model of tumor dissemination
Alonso-Alconada et al. 2014
Hec-1A cell line; FFPE sections from human ECs and tumors originated from Hec-1A and Hec-1A GFP-ERM/ETV5 cells orthtopically implanted in mice Tumor samples (n=15); Ishikawa and
Monge et al. 2009
Liao et al. 2014
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detected between SHARP1 and E-cadherin levels; negative correlation between SHARP1 and vimentin, SNAIL and JAG1. Notch pathway has a tumor-suppressive role in human EC cells.
Notch1-JAG1 axis enhances the invasiveness and motility of EC cells.
Eph receptor signaling
FOXA1 transcription factor activates Notch pathway; a functional role for FOXA1 in mediating migration and invasion in EC cells has been suggested. Switch in FOXA1expression from primary to metastatic lesion associates with EC progression and correlates with CDKN2A expression in metastasis. PPAR/RXR pathway contributes to endometrial carcinogenesis by control of PTEN expression and modulating VEGF secretion.
PPARg agonist rosiglitazone inhibits proliferation and induces apoptosis in a mouse model of endometrial hyperplasia. Role for EphA2 as a regulator in relation to EMT in EC has been suggested. EphA2 overexpression observed in EEC correlates with advanced disease, lack of hormone receptor expression and poor prognosis. Over expression of EphA2 is associated with markers of angiogenesis and correlates with aggressive clinical features.
Loss of ARID1A expression observed exclusively in EEC and cooccurrs with alterations in the PI3K-Akt pathway. Loss of ARID1A an early event in carcinogenesis of EEC and correlates with deep myometrial infiltration. No relation between gene signatures for EMT and ARID1A expression observed. ARID1A loss more common in high-grade EEC and associates with mismatch protein deficiency and normal p53 expression. ARID1A expression is associated with the differentiation status , ER and p53 but not clinical stage, depth of myometrial invasion, lymph node metastasis and overall patient survival Role of SWI/SNF subunit alterations in the progression/dedifferentiation of EC suggested. SWI/SNF and MMR protein deficiencies may act synergistically in deregulating DNA repair mechanisms.
HEC-1B cell lines
Tumor (Stage1) and adjacent non tumor tissue (n=22) Tumor samples (stages I, III and IV, n=76); Ishikawa, HHUA, Hec-1A, Hec-1B and KLE cell lines Tissue samples from AH and EC (n=87); AN3CA, RL95-2 and HEC-1B cell lines; mouse tumor xenograft model Tissue samples from primary (n=529) and metastatic (n=199) lesions
Sasnauskiene et al. 2014 Mitsuhashi et al. 2012
Tissue samples from benign and EC (grades 1,2 and 3) (n=20); Ishikawa and HEC-1A cell lines HEC1A and Ishikawa cell lines; PTEN heterozygote murine model
Nickkho-Amiry et al. 2012
Qiu et al. 2014
Tangen et al. 2014
Wu et al. 2008
Tissue samples (EEC, n=139 and benign, n=10) Tumor samples (n=85); HEC1A, HEC1B and Ishikawa cell lines; orthotopic mouse model FFPE samples of primary ECs (n=146)
Kamat et al. 2009
Tissue samples from primary EC (n=535), metastatic lesions (n=77) and EH (n=38)
Werner et al. 2013
Tissue samples from high grade endometrial cancers (n=190) Tissue samples, EC (n=74; stages I to IV), CH (n=20), AH (n=20) and normal endometrium (n=20) 22 undifferentiated EC out of which 17 were dedifferentiated
Allo et al. 2014
Merritt et al. 2010
Bosse et al. 2013
Zhang et al. 2014
Stewart & Crook 2015
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SWI/SNF complex is involved in the pathogenesis of dedifferentiation of EEC in a subset of cases and correlates with aggressive rhabdoid phenotype. Epigenetic modifications and miRNA regulation DNA methylation DNA methylation changes regulate gene expression not only by affecting proximal promoters but also distant enhancers and /demethylation; transposable elements. histone acetylation/deacetylatio Gene hypermethylation may be an early event in endometrial n endometrioid tumorigenesis. While ER-A, PR, hMLH1, CDKN2A/P16, CDH1/E-CADHERIN, SFRP1, SFRP2, SFRP5 show promoter methylation status in EEC, SFRP4 shows demethylation. Loss of PR-B and progesterone responsiveness leads to methylation of HOXA10 promoter, activation of SNAIL, inhibition of E-cadherin, increased invasion and tumor dissemination. CDH13, RASSF1A, and GSTP1 are the most frequently methylated genes in endometrial hyperplasia and carcinoma.
Epigenetic inactivation of EFEMP1inhibits tumor growth and invasion. Ectopic EFEMP1 expression is associated with EMT, most likely by perturbing extracellular matrix.
Downregulation of tumor suppressor EMX2 is a critical factor in the carcinogenesis and progression of EC.
Loss of tumor suppressor ARID1A is associated with deep myometrial invasion and is an early event in the carcinogenesis of EEC.
EZH2overexpression is associated with EC invasion and metastasis. Inhibition of EZH2 decreases proliferation, migration and invasion either by upregulation of E-cadherin or inactivation of Wnt/B-catenin signaling. EZH2 expression is an early event in EC carcinogenesis. Overexpression of EZH2 correlates with deep myometrial invasion, LVSI and enhanced cell proliferation of EC cells. EZH2 may regulate EC migration along with FAK through modulation of E-cadherin. The entire miR-200 family is up-regulated in EEC, implicated in the
Poorly differentiated (grade 3) and undifferentiated tumor samples (n=26)
Primary endometrial tumor samples (EAC-1, EAC-2, EAC-3, UPSC-1, UPSC-2 and UPSC-3) Benign, premalignant and malignant endometrial lesions (n=39)
SPEC2 and KLE cell lines ; tumor samples (Grades 1,2,3 EEC, n=121, and UPSC n=30) Tissue samples (normal, SH, CH, CAH, EC ) in mutation positive/negative, EC positive/negative, sporadic groups (n=172) FFPE samples (normal, AH, and EC, n=134), Fresh frozen EC tissues (n=97); HEC-1B, RL95-2, ISK, SPEC2, AN3CA and KLE cell lines Tissue samples (EC n=122 and normal n=25); Ishikawa, KLE, AN3CA and SPEC2 cell lines FFPE tissues of primary EC (n=535), metastatic lesions (n=77), hyperplasia (n=38); fresh frozen primary tumors (n=122) ECC-1, RL95-2, HEC-1A and T-HESC cell lines; FFPE EC tissue (n=40)
Strehl et al. 2015
Zhang et al. 2014
Di Domenico et al. 2011
Yoshida et al. 2006
Nieminen et al. 2009
Yang et al. 2013
Qiu et al. 2013
Werner et al. 2013
Eskander et al. 2013
Tissue samples (normal, SH, CH, AH and EC) (n=92).HEC1A and Ishikawa cell lines.
Jia et al. 2014
FFPE tumor samples (type I n=141, type II n=61))
Zhou et al.2013
FFPE samples of CAH, EEC and PE
Snowdon et al. 2011
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EMT process by negatively regulating ZEB1 and ZEB2. Alterations in endometrial miR-200c observed during transformation into cancerous states and target the expression of ZEBs, VEGFA, FLT1, IKKB, KLF9, and FBLN5.
Up regulated expression of all members of miR-200 family observed in all stages of EEC. miR-206 overexpression inhibits ER-A dependent cell proliferation, impairs invasiveness and induces cell cycle arrest in EEC cell line.
Elevated miR-222-3p expression promotes proliferation, invasion, G1 to S phase transition and increases raloxifene resistance by suppressing ER-A expression in EC cells. Aberrant expression of miR-200b, miR-130a/b, miR-625 and miR-222 associated with tumorigenesis and metastasis. Ectopic expression of miR-130b and knockdown of DICER1 increased the expression of Vimentin, ZEB2, N-cadherin, Twist and Snail. miR-205 promotes cellular proliferation, migration and invasion of EEC through targeting estrogen-related receptor-gamma. miR-194 expression was lower in EEC patients with more advanced stage. It regulates EMT by suppressing expression of BMI-1. miR-31overexpression promotes anchorage-independent growth in vitro and increases the tumor forming potential in vivo.
miR-214 is differentially expressed in FIGO stage I and controls PTEN expression. miR-18a is differentially expressed in FIGO stage II and regulates KRAS. miR-148b and miR-335 regulate members of the Wnt pathway. miR-17 and miR-34a regulate BCL2 and CCND1 genes involved in PI3K/Akt signaling. miR-199a-3p inhibits EEC cell proliferation through negative regulation of mTOR expression. miR promotes cell apoptosis and senescence, suppresses EMT and CSC properties of aggressive EC cells.
hsa-miR-181a plays an oncogenic role in endometrial tumorigenesis and is a critical regulator of tumor metastasis in advanced EC.
CAFs promote EC cell proliferation, in part by modulating PI3K/Akt and MAPK/ERK pathways.
(n=34) Endometrial samples from EC (n=17), normal (n=35), perimenopausal (n=3), postmenopausal (n=2), Depo-Provera (n=5); Ishikawa cell line Tissue samples (EAC, FIGO stages I, II and III, n=30; PE and SE, n=20) RL95-2, Ishikawa and KLE cell lines;Tissue samples (EEC, n=30, SE and PE, n=20) Tumor samples (n=75); RL95-2, AN3CA and KLE cell lines; mouse xenograft model Ishikawa and AN3Ca cell lines
Panda et al. 2012
Jurcevic et al. 2014
Chen et al. 2012
Liu et al. 2014
Li et al. 2013
Tissue samples (normal n=22 and EEC n=53); Ishikawa, KLE and AN3CA cells HHUA, HOUA-I and HEC-50B cell lines
Su et al. 2013
Tumor samples (Stages I-IV)(n=34); HEC-50B, HEC-1A and HEC-108 cell lines Tissue samples (EAC, FIGO stages I, II and III, n=30; PE and SE, n=20)
Mitamura et al. 2014
EEC and paired adjacent nontumor tissue (n=10); Ishikawa cells HEC-50, HOUA-I, SPAC-1-L, SPAC-1-S and EM cell lines. Tumor samples (Grade 3 EEC, n=50) Primary epithelial and stromal cells from human endometrial tissues (EC and EH, n=47); ECC-1, Hec-1A and T-HESC cells
Wu et al. 2013
Tissue samples (EC n=4; EH n=1)
Dong et al. 2011
Jurcevic et al. 2014
Konno et al. 2014
He et al. 2015
Subramaniam et al. 2013
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Silencing of miR-148a in CAFs from EC patients results in WNT10Bmediated stimulation of tumor motility. CAFs stimulate progression of malignancy through the release of SDF1. Increased expression of SDF-1 was associated with a more aggressive phenotype of the tumor. MELF invasion represents an active cellular event during EC invasion. Upregulation of cyclin D1 and p16, together with loss of membranous B-catenin expression observed in tumor foci composed of MELF glands. KRAS mutations are more frequent in MELF positive than MELF negative tumors. MELF changes represent areas of active tumor invasion. MELF pattern of myometrial invasion shows significant association with lymph node metastasis. Cases with MELF-pattern show an increased rate of lymph node metastasis even within the subset of EEC with lymphvascular space invasion.
Primary endometrial fibroblast cells; ACI-158, EC1 and ACI-98 cell lines Tumor samples (n=92) (Stages 1A, IB, II, IIIA, IIIC and IV)
Aprelikova et al. 2013
Tumor samples EEC (n=21) Tumor samples with MELF type of myometrial invasion (n=22)
Stewart and Little 2009 Stewart et al. 2009
MELF positive (n=33) and MELF negative (n=33) low grade EECs
Stewart et al. 2010
Tumor samples (n=351)
T1 stage EEC with LVSI and associated lymph node dissection (n=80)
Walentowicz-Sadlecka et al. 2014
Stewart et al. 2011 Pavlakis et al. 2011
Hertel et al. 2014
Abbreviations: SH-simple hyperplasia, AH-atypical hyperplasia, EH-endometrial hyperplasia, CH-complex hyperplasia, CAHcomplex atypical hyperplasia, CAFs-cancer-associated fibroblasts, EACs-endometrial adenocarcinomas, EEC-endometrioid endometrial carcinoma, FFPE-formalin fixed paraffin embedded, LVSI- lymphvascular space invasion, PE-proliferative endometrium, SE-secretory endometrium. *Tissue/Tumor samples mentioned in the table were human samples unless otherwise specified
Tumor progression, metastasis and modulators of EMT in ...
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Accepted Preprint first posted on 4 November 2015 as Manuscript ERC-15-0218
Tumor progression, metastasis and modulators of EMT in e...
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