How does tgf beta induced emt

Kong, M. Effects of polyphyllin I on growth inhibition of human non-small lung cancer cells and in xenograft. Kong, S. Black rice bran as an ingredient in noodles: chemical and functional evaluation. Kou, Y. Kulkarni, S. Berberine: a plant alkaloid with therapeutic potential for central nervous system disorders. Steady-State pharmacokinetics and tolerability of trans-resveratrol mg twice daily with food, quercetin and alcohol ethanol in healthy human subjects.

Lee, D. Anti-proliferative effects of ginsenosides extracted from mountain ginseng on lung cancer. Lee, J. Withaferin a inhibits experimental epithelial-mesenchymal transition in MCFA cells and suppresses vimentin protein level in vivo in breast tumors.

Anti-inflammatory effects of magnolol and honokiol are mediated through inhibition of the downstream pathway of MEKK-1 in NF-kappaB activation signaling. Planta Med. The epithelial-mesenchymal transition: new insights in signaling, development, and disease. Genistein as a potential anticancer agent against ovarian cancer. Lee, I. Phenolic compounds from Duchesnea chrysantha and their cytotoxic activities in human cancer cell.

Li, J. A novel anti-cancer effect of resveratrol: reversal of epithelial-mesenchymal transition in prostate cancer cells. Chemical constituents from the stems of Celastrus orbiculatus.

ISSN The effects of ginsenoside Rb1 on JNK in oxidative injury in cardiomyocytes. Li, W. Cryptotanshinone, a Stat3 inhibitor, suppresses colorectal cancer proliferation and growth in vitro. Cell Biochem. Li, X. Liappas, G. Lin, C. Lin, D. Lin, X. ShaoYao decoction ameliorates colitis-associated col- orectal cancer by downregulating proinflammatory cytokines and promoting epithelial-mesenchymal transition.

Lin, Y. Luteolin, a flavonoid with potential for cancer prevention and therapy. Cancer Drug Targets 8, — Lin, L. Celastrol ameliorates ulcerative colitis-related colorectal cancer in mice via suppressing inflammatory responses and epithelial-mesenchymal transition. Liu, D. Piperlongumine suppresses bladder cancer invasion via inhibiting epithelial mesenchymal transition and F-actin reorganization.

Liu, L. Liu, Q. Piperlongumine inhibits migration of glioblastoma cells via activation of ROS-dependent p38 and JNK signaling pathways. Oxidative Med. Liu, Y. Epithelial to mesenchymal transition in renal fibrogenesis: pathologic significance, molecular mechanism, and therapeutic intervention.

Liu, C. Effects of berberine on amelioration of hyperglycemia and oxidative stress in high glucose and high fat diet-induced diabetic hamsters in vivo. PLoS One 11 3 , e Liu, P. Resveratrol inhibits human lung adenocarcinoma cell metastasis by suppressing heme oxygenase 1-mediated nuclear factor-kappaB pathway and subsequently downregulating expression of matrix metalloproteinases. Liu, X. The effects of genistein and puerarin on the activation of nuclear factor-kappaB and the production of tumor necrosis factor-alpha in asthma patients.

Pharmazie 65 2 , — Lopez-Cabrera, M. Mesenchymal conversion of mesothelial cells is a key event in the pathophysiology of the peritoneum during peritoneal dialysis. Lou, W. Lovisa, S. Epithelial-to-mesenchymal transition induces cell cycle arrest and parenchymal damage in renal fibrosis.

Lu, Z. Exploring brusatol as a new anti-pancreatic cancer adjuvant: biological evaluation and mechanistic studies. Oncotarget 8 49 , — Lu, L. Beneficial effects exerted by paeonol in the management of atherosclerosis. Cell Longev. Lv, X. Ma, S. Cryptotanshinone attenuates isoprenaline-induced cardiac fibrosis in mice associated with upregulation and activation of matrix metalloproteinase Ma, Y.

Marin-Neto, J. Cardiovascular effects of berberine in patients with severe congestive heart failure. EMBO 19, — How cells read TGF-beta signals. Masszi, A. Central role for Rho in TGF-beta1-induced alpha-smooth muscle actin expresion during epithelial-mesenchymal transition. Renal Physiol. Smaddening complexity: the role of Smad3 in epithelial-myofibroblast transition. Cells Tissues Organs , 41— McCubrey, J.

Effects of resveratrol, curcumin, berberine and other nutraceuticals on aging, cancer development, cancer stem cells and microRNAs. Aging Albany N. Mohsenikia, M. The protective and therapeutic effects of alpha-solanine on mice breast cancer. Morikawa, T. Bioactive constituents from Chinese natural medicines. Moshiri, A. Acta Gene Regul Mech. Nagalingam, A. Honokiol activates AMP-activated protein kinase in breast cancer cells via an LKB1-dependent pathway and inhibits breast carcinogenesis.

Breast Cancer Res. Newman, D. Natural products as sources of new drugs over the last 25 years. Nieto, M. EMT: Cell , 21— Ninomiya, K. Absolute structures of new megastigmane glycosides, sedumosides A 4 , A 5 , A 6 , H, and I, and hepatoprotective megastigmanes from Sedum sarmentosum. Oh, H. Isolation of angiotensin converting enzyme ACE inhibitory flavonoids from Sedum sarmentosum. Ong, R. Polyphyllin D induces mitochondrial fragmentation and acts directly on the mitochondria to induce apoptosis in drugresistant HepG2 cells.

Padhye, S. Perspectives on medicinal properties of plumbagin and its analogs. Padmavathi, B. Roots of Withania somnifera inhibit forestomach and skin carcinogenesis in mice. Pan, S. Plumbagin suppresses epithelial to mesenchymal transition and stemness via inhibiting Nrf2-mediated signaling pathway in human tongue squamous cell carcinoma cells. Drug Des. Pattarayan, D. Cell Physiol. Patwardhan, C.

Gedunin inactivates the co-chaperone p23 protein causing cancer cell death by apoptosis. Peinado, H. Transforming growth factor b-1 induces snail transcription factor in epithelial cell lines. Peng, C. Abelmoschus esculentus fractions potently inhibited the pathogenic targets associated with diabetic renal epithelial to mesenchymal transition.

Food Funct. Petpiroon, N. Popat, R. A phase 2 study of SRT resveratrol with bortezomib for patients with relapsed and or refractory multiple myeloma. Poser, I. Loss of E-cadherin expression in melanoma cells involves up-regulation of the transcriptional repressor snail. Qian, Y. Celastrus orbiculatus extract inhibits tumor angiogenesis by targeting vascular endothelial growth factor signaling pathway and shows potent antitumor activity in hepatocarcinomas in vitro and in vivo.

Qiao, W. Two new triterpenes from Duchesnea indica. Qu, Y. Protective role of gambogic acid in experimental pulmonary fibrosis in vitro and in vivo. Phytomedicine 23 4 , — Raj, L. Selective killing of cancer cells by a small molecule targeting the stress response to ROS.

Nature , e Rastaldi, M. Epithelial-mesenchymal transition and its implications for the development of renal tubulointerstitial fibrosis. Russo, M. Sirtuins and resveratrol-derived compounds: a model for understanding the beneficial effects of the Mediterranean diet. Immune Disord. Drug Targets 14 4 , — Ryu, Y. Gallic acid prevents isoproterenol-induced cardiac hypertrophy and fibrosis through regulation of JNK2 signaling and Smad3 binding activity, Sci.

Sarkar, S. Cancer 21 1 , — Sato, M. Savagner, P. The epithelial-mesenchymal transition EMT phenomenon. Sehitoglu, M. Anthocyanins: targeting of signaling networks in cancer cells. Asian Pac. Shakibaei, M. Resveratrol addiction: to die or not to die.

Shankar, S. Resveratrol inhibits pancreatic cancer stem cell characteristics in human and KrasG12D transgenic mice by inhibiting pluripotency maintaining factors and epithelial-mesenchymal transition. PLoS One 1 , e Sharma, R. Phase I clinical trial of oral curcumin: biomarkers of systemic activity and compliance. Shen, K. Molecules 8 , — Shen, X. Asian Nat. Sheu, M. Inhibition of NADPH oxidase-related oxidative stress-triggered signaling by honokiol suppresses high glucose-induced human endothelial cell apoptosis.

Shi, G. Effects of oxymatrine on experimental hepatic fibrosis and its mechanism in vivo. World J. Shibata, S. Song, Y. Plant-derived natural products as leads to anti-cancer drugs. Plant Herb. Su, N. Metronomic cordycepin therapy prolongs survival of oral cancer-bearing mice and inhibits epithelial-mesenchymal transition. Molecules 22, Subramani, R. Nimbolide inhibits pancreatic cancer growth and metastasis through ROS-mediated apoptosis and inhibition of epithelial-to-mesenchymal transition.

Gedunin inhibits pancreatic cancer by altering sonic hedgehog signaling pathway. Oncotarget 8 7 , — Sun, L. Curcumin ameliorates epithelial-to mesenchymal transition of podocytes in vivo and in vitro via regulating caveolin Sun, M.

Nitidine chloride induces apoptosis, cell cycle arrest, and synergistic cytotoxicity with doxorubicin in breast cancer cells. Tumour Biol. Hedgehog pathway is involved in nitidine chloride induced inhibition of epithelial-mesenchymal transition and cancer stem cells-like properties in breast cancer cells.

Cell Biosci. Sutariya, Brijesh, S. Tan, C. Integrin-linked kinase regulate inducible nitric oxide synthase and cyclooxygenase-2 expression in an NF-kB-dependent manner. Thiery, J.

Epithelialmesenchymal transitions in development and disease. Cell , — Tillhon, M. Berberine: new perspectives for old remedies. Troussard, A. Oncogene 16, — Tsai, J. Unahabhokha, T. The attenuation of epithelial to mesenchymal transition and induction of anoikis by gigantol in human lung cancer H cells. Vega, S. Snail blocks the cell cycle and confers resistance to cell death. Venkatesha, S. Celastrus-derived celastrol suppresses autoimmune arthritis by modulating antigen-induced cellular and humoral effector responses.

Vergara, D. Resveratrol inhibits the epidermal growth factor-induced epithelial mesenchymal transition in MCF-7 cells. Antitumor activity of the dietary diterpene carnosol against a panel of human cancer cell lines. Endocardial and epicardial epithelial to mesenchymal transitions in heart development and disease.

Vuddanda, P. Berberine: a potential phytochemical with multispectrum therapeutic activities. Expert Opin. Drugs 19, — Wallerath, T. Resveratrol, a polyphenolic phytoalexin present in red wine, enhances expression and activity of endothelial nitric oxide synthase. Circulation 13 , — Wang, J. Wang, Z. Wang, H. Wang, D.

Celastrus orbiculatus extract suppresses the epithelial-mesenchymal transition by mediating cytoskeleton rearrangement via inhibition of the Cofilin 1 signaling pathway in human gastric cancer.

Wang, W. Oncotarget 9 42 , — Wen, Y. By inhibiting snail signaling and miRa-3p, osthole suppresses the EMT-mediated metastatic ability in prostate cancer. Oncotarget 6 25 , — Widodo, N. Selective killing of cancer cells by leaf extract of Ashwagandha: identification of a tumor-inhibitory factor and the first molecular insights to its effect.

White, C. The impact of turmeric or its curcumin extract on nonalcoholic fatty liver disease: a systematic review of clinical trials. Granada 17 1 , Wong, K. Tripterygium wilfordii bioactive compounds as anticancer and anti-inflammatory agents.

Wrighton, K. Phospho-control of TGF-beta superfamily signaling. Cell Res. Wu, L. Wu, X. Xiao, Z. Resveratrol attenuates renal injury and fibrosis by inhibiting transforming growth factor-beta pathway on matrix metalloproteinase 7.

Xiao, S. Celastrol synergizes with oral nifedipine to attenuate hypertension in preeclampsia: a randomized, placebo-controlled, and double blinded trial.

Xing, S. Xu, T. PLoS One 9 7 , e Xu, Y. Xu, Q. Resveratrol in the treatment of pancreatic cancer. Xu, J. Clinical analysis of the preventive effect of Schisandra chinensis on anti-tuberculosis therapy induced liver injury. Yichun College 36 6 , 65— Peritoneal dialysis and epithelial-to-mesenchymal transition of mesothelial cells. Yan, F. Glucagon-like Peptide 1 protects against hyperglycemic-induced endothelial-to-mesenchymal transition and improves myocardial dysfunction by suppressing Poly ADP-Ribose polymerase 1 activity.

Yang, Y. Resveratrol analog-3,5,4-trimethoxytrans-stilbene inhibits invasion of human lung adenocarcinoma cells by suppressing the MAPK pathway and decreasing matrix metalloproteinase-2 expression.

Yang, L. Yang, M. Curcumin in autoimmune and rheumatic diseases. Nutrients 2, 11 5. Yin, J. Efficacy of berberine in patients with type 2 diabetes mellitus. Metabolism 57 5 , — Yoo, K. Osteopontin regulates renal apoptosis and interstitial fibrosis in neonatal chronic unilateral ureteral obstruction. Kidney Int. Yu, Q. Polyphyllin D induces apoptosis in U87 human glioma cells through the c-Jun NH2-terminal kinase pathway.

Sponsored Conferences. Impact Journals is a member of the Society for Scholarly Publishing. Epithelial to mesenchymal transition EMT is a progression of cellular plasticity critical for development, differentiation, cancer cells migration and tumor metastasis. These results implicate that ANCR might become a prognostic biomarker and an anti-metastasis therapy target for breast cancer.

Breast cancer is the most common cancer in women worldwide [ 1 , 2 ], and the distance metastasis is the major cause for the breast cancer mortality [ 3 , 4 ]. The epithelial-mesenchymal transition EMT program was first found in embryonic development. EMT program induces cell-cell conjunctions decreasing and down-regulation of epithelial marker E-cadherin , while it promotes cell motility and increases the expression of mesenchymal markers N-cadherin, Vimentin, Fibronectin.

EMT program has also been proven to play a core part in breast cancer cell migration and metastasis in breast cancer patients [ 5 , 6 ]. LncRNAs have many effects on human diseases, cell proliferation, differentiation and cancer cells migration [ 16 — 19 ]. Studies have shown that some lncRNAs play central roles in tumor metastasis [ 16 ]. ANCR is indispensable to enforce the undifferentiated cell state within epidermis [ 17 ]. This study aimed to further elucidation of the physiological and pathological functions of ANCR in breast cancer metastasis.

RUNX2 is known for its contribution to osteoblast phenotype and bone formation. In recent years, increasing attention has been focused on the relationship of RUNX2 and tumorigenesis [ 26 — 31 ].

Expression and function of RUNX2 have been implicated in various human cancers, especially in breast cancer. RUNX2 and its target genes are highly expressed in breast cancer tissues and play pivotal roles in breast cancer bone metastasis [ 30 , 32 — 36 ].

In addition, we uncovered a negatively correlated expression pattern between ANCR and RUNX2 in breast cancer tissues and several breast cancer cell lines. Overall, data from our study identify a novel mechanism of ANCR function by participating in EMT and metastasis, and provide a new clue for the diagnosis and treatment of breast cancer.

We then examined both the epithelial and mesenchymal markers by using western blotting. These results suggest that ANCR might be regulated by acetylation modification of histones. It is well known that RUNX2 is a core transcription factor regulating many kinds of cell differentiation [ 19 , 42 , 43 ].

Furthermore, we intended to evaluate the pathological relevance between ANCR and tumor metastasis in breast cancer in vivo. A-B Representative bioluminescence images of lung metastasis in mice injected with cells as indicated via tail veins, and the metastasis were quantified by measuring the photo flux. The white arrows denoted the metastatic nodules.

F Representative images of the immunohistochemical staining of RUNX2 in nude mice lung metastasis sections. Subsequently, the lung tissue sections were prepared and examined after staining with hematoxylin and eosin, and we detected smaller and fewer metastatic foci in the tissues from nude mice injected with MDA-MBANCR cells Figure 7E. Taken together, these data suggests that ANCR is able to inhibit RUNX2 expression, which plays a pivotal role in repression of breast cancer metastasis in vivo.

RUNX2 is known to be frequently up-regulated in breast cancer patients, and higher RUNX2 level often leads to the poor prognosis of patients [ 33 , 36 , 38 ]. As can be seen, ANCR exhibited an apparently lower level in tumor tissues compared with the adjacent normal tissues Figure 8A. We also found that the expression of ANCR was lower in breast cancer tissues compared with the matched normal adjacent tissues, indicating that ANCR may act as a tumor suppressor. Acetylation is a core modification of histones in regulation of gene transcription.

Our results suggest that ANCR probably can directly regulate RUNX2 transcriptional expression, but the detailed insight of mechanism needs further study. And our collected samples from breast cancer tissues and adjacent tissues is not so many. In the future, these experiments with larger sample size from cancer tissues, adjacent tissues as well as normal tissues will be further conducted to improve our preliminary work and clarify the molecular mechanisms in depth.

Above all, our findings provide a novel insight into the functional role of the ANCR-driven anti-tumorigenesis. Samples were frozen in liquid nitrogen immediately after surgery. Breast tissue specimens were collected using the protocols approved by the Ethics Committee of the Jilin Oncology Hospital.

Western Blot, plasmids and virus infection have been shown in our Supplementary Information. Nucleic Acids Res. G9a and histone deacetylases are crucial for Snail2-mediated E-cadherin repression and metastasis in hepatocellular carcinoma. Cancer Sci. Biochem Biophys Res Commun.

PLoS One. Role of RbBP5 and H3K4me3 in the vicinity of snail transcription start site during epithelial-mesenchymal transition in prostate cancer cell. EZH2 inhibition promotes epithelial-to-mesenchymal transition in ovarian cancer cells.

Epigenetics Chromatin. Article Google Scholar. Histone 3 lysine 9 H3K9 methyltransferase recruitment to the interleukin-2 IL-2 promoter is a mechanism of suppression of IL-2 transcription by the transforming growth factor-b-Smad pathway.

J Pathol. Cancer Res. Identification of the transition states during EMT. Pastushenko I, Blanpain C. EMT transition states during tumor progression and metastasis. Trends Cell Biol. A comprehensive DNA methylation profile of epithelial-to-mesenchymal transition. A pooled single-cell genetic screen identifies regulatory checkpoints in the continuum of the epithelial-to-mesenchymal transition.

Nat Genet. ATAC-seq: a method for assaying chromatin accessibility genome-wide. Curr Protoc Mol Biol. An evaluation of 3C-based methods to capture DNA interactions. Nat Methods.

Comprehensive mapping of long-range interactions reveals folding principles of the human genome. RNA m6A methylation regulates the epithelial mesenchymal transition of cancer cells and translation of snail. Download references. Due to the limitation of space, we apologize to the authors whose papers were not cited in the manuscript. This work was supported in part to K. You can also search for this author in PubMed Google Scholar.

The authors read and approved the final manuscript. Correspondence to Kou-Juey Wu. All the authors agreed to participate in the writing of the manuscript. This is a review article.

Therefore, no ethics committee that is required to approve any study. There is also no animal study involved and no approved consent from a client is required. All the authors have viewed the manuscript and agree with the submission of this manuscript. Therefore, no individual data in any form is included inside the manuscript.

No consent from any such person is required. Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Reprints and Permissions. Lin, YT. J Biomed Sci 27, 39 Download citation. Received : 22 December Accepted : 18 February Published : 02 March Anyone you share the following link with will be able to read this content:.

Sorry, a shareable link is not currently available for this article. Provided by the Springer Nature SharedIt content-sharing initiative. Skip to main content. Search all BMC articles Search. Download PDF. Abstract Epithelial-mesenchymal transition EMT is an important process triggered during cancer metastasis. Introduction Epithelial-mesenchymal transition EMT is one of the initial and crucial mechanisms causing cancer metastasis [ 1 , 2 , 3 ]. Epigenetic regulation of hypoxia-induced EMT: focusing on H3K4Ac histone mark and immune suppression Hypoxia is one of the crucial microenvironmental factors that induces cancer metastasis [ 16 , 17 ].

Conclusion Since epithelial-mesenchymal transition is an important initial mechanism to mediate tumor metastasis, delineation of its molecular mechanisms will be key to handling tumor metastasis and treatment resistance derived from EMT. Full size image. Availability of data and materials Since the paper is a review article, there is no supporting experimental data.

References 1. Google Scholar Article Google Scholar Acknowledgments Due to the limitation of space, we apologize to the authors whose papers were not cited in the manuscript. Funding This work was supported in part to K.

View author publications. Ethics declarations Ethics approval and consent to participate All the authors agreed to participate in the writing of the manuscript.

Consent for publication All the authors have viewed the manuscript and agree with the submission of this manuscript.

Competing interests The authors declare that they have no competing interests. About this article. Cite this article Lin, YT. Copy to clipboard.