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Article ; Online: Beyond TGFβ: roles of other TGFβ superfamily members in cancer.

Wakefield, Lalage M / Hill, Caroline S

2013 Volume 13, Issue 5, Page(s) 328–341

Abstract: Much of the focus on the transforming growth factor-β (TGFβ) superfamily in cancer has revolved around the TGFβ ligands themselves. However, it is now becoming apparent that deregulated signalling by many of the other superfamily members also has crucial ...

Abstract	Much of the focus on the transforming growth factor-β (TGFβ) superfamily in cancer has revolved around the TGFβ ligands themselves. However, it is now becoming apparent that deregulated signalling by many of the other superfamily members also has crucial roles in both the development of tumours and metastasis. Furthermore, these signalling pathways are emerging as plausible therapeutic targets. Their roles in tumorigenesis frequently reflect their function in embryonic development or in adult tissue homeostasis, and their influence extends beyond the tumours themselves, to the tumour microenvironment and more widely to complications of cancer such as cachexia and bone loss.
MeSH term(s)	Animals ; Cell Differentiation ; Cell Proliferation ; Embryonic Development ; Humans ; Molecular Targeted Therapy ; Neoplasms/drug therapy ; Neoplasms/metabolism ; Neoplasms/pathology ; Neoplastic Stem Cells/physiology ; Protein Processing, Post-Translational ; Signal Transduction ; TGF-beta Superfamily Proteins/physiology ; Tumor Microenvironment
Chemical Substances	TGF-beta Superfamily Proteins
Language	English
Publishing date	2013-04-18
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2062767-1
ISSN	1474-1768 ; 1474-175X
ISSN (online)	1474-1768
ISSN	1474-175X
DOI	10.1038/nrc3500
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Article ; Online: Capillary nano-immunoassays: advancing quantitative proteomics analysis, biomarker assessment, and molecular diagnostics.

Chen, Jin-Qiu / Wakefield, Lalage M / Goldstein, David J

Journal of translational medicine

2015 Volume 13, Page(s) 182

Abstract: There is an emerging demand for the use of molecular profiling to facilitate biomarker identification and development, and to stratify patients for more efficient treatment decisions with reduced adverse effects. In the past decade, great strides have ... ...

Abstract	There is an emerging demand for the use of molecular profiling to facilitate biomarker identification and development, and to stratify patients for more efficient treatment decisions with reduced adverse effects. In the past decade, great strides have been made to advance genomic, transcriptomic and proteomic approaches to address these demands. While there has been much progress with these large scale approaches, profiling at the protein level still faces challenges due to limitations in clinical sample size, poor reproducibility, unreliable quantitation, and lack of assay robustness. A novel automated capillary nano-immunoassay (CNIA) technology has been developed. This technology offers precise and accurate measurement of proteins and their post-translational modifications using either charge-based or size-based separation formats. The system not only uses ultralow nanogram levels of protein but also allows multi-analyte analysis using a parallel single-analyte format for increased sensitivity and specificity. The high sensitivity and excellent reproducibility of this technology make it particularly powerful for analysis of clinical samples. Furthermore, the system can distinguish and detect specific protein post-translational modifications that conventional Western blot and other immunoassays cannot easily capture. This review will summarize and evaluate the latest progress to optimize the CNIA system for comprehensive, quantitative protein and signaling event characterization. It will also discuss how the technology has been successfully applied in both discovery research and clinical studies, for signaling pathway dissection, proteomic biomarker assessment, targeted treatment evaluation and quantitative proteomic analysis. Lastly, a comparison of this novel system with other conventional immuno-assay platforms is performed.
MeSH term(s)	Biomarkers/analysis ; Electrophoresis, Capillary/methods ; Humans ; Immunoassay/methods ; Nanotechnology/methods ; Pathology, Molecular/methods ; Proteomics/methods
Chemical Substances	Biomarkers
Keywords	covid19
Language	English
Publishing date	2015-06-06
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Intramural ; Review
ISSN	1479-5876
ISSN (online)	1479-5876
DOI	10.1186/s12967-015-0537-6
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Article ; Online: Peptidylarginine Deiminase IV Regulates Breast Cancer Stem Cells via a Novel Tumor Cell-Autonomous Suppressor Role.

Moshkovich, Nellie / Ochoa, Humberto J / Tang, Binwu / Yang, Howard H / Yang, Yuan / Huang, Jing / Lee, Maxwell P / Wakefield, Lalage M

Cancer research

2020 Volume 80, Issue 11, Page(s) 2125–2137

Abstract: Peptidylarginine deiminases (PADI) catalyze posttranslational modification of many target proteins and have been suggested to play a role in carcinogenesis. Citrullination of histones by PADI4 was recently implicated in regulating embryonic stem and ... ...

Abstract	Peptidylarginine deiminases (PADI) catalyze posttranslational modification of many target proteins and have been suggested to play a role in carcinogenesis. Citrullination of histones by PADI4 was recently implicated in regulating embryonic stem and hematopoietic progenitor cells. Here, we investigated a possible role for PADI4 in regulating breast cancer stem cells. PADI4 activity limited the number of cancer stem cells (CSC) in multiple breast cancer models
MeSH term(s)	Animals ; Breast Neoplasms/enzymology ; Breast Neoplasms/genetics ; Breast Neoplasms/pathology ; Cell Line, Tumor ; Disease Progression ; Female ; Gene Knockdown Techniques ; Humans ; Isoenzymes ; MCF-7 Cells ; Mice ; Nanog Homeobox Protein/genetics ; Nanog Homeobox Protein/metabolism ; Neoplastic Stem Cells/enzymology ; Neoplastic Stem Cells/pathology ; Octamer Transcription Factor-3/genetics ; Octamer Transcription Factor-3/metabolism ; Protein-Arginine Deiminase Type 4/antagonists & inhibitors ; Protein-Arginine Deiminase Type 4/genetics ; Protein-Arginine Deiminase Type 4/metabolism ; Transcription Factors/genetics ; Transcription Factors/metabolism ; Transcriptome
Chemical Substances	Isoenzymes ; NANOG protein, human ; Nanog Homeobox Protein ; Octamer Transcription Factor-3 ; POU5F1 protein, human ; Transcription Factors ; PADI4 protein, human (EC 3.5.3.15) ; Protein-Arginine Deiminase Type 4 (EC 3.5.3.15)
Language	English
Publishing date	2020-04-07
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Intramural
ZDB-ID	1432-1
ISSN	1538-7445 ; 0008-5472
ISSN (online)	1538-7445
ISSN	0008-5472
DOI	10.1158/0008-5472.CAN-19-3018
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Article: Synergistic antitumor effects of a TGFβ inhibitor and cyclophosphamide.

Chen, Xin / Wakefield, Lalage M / Oppenheim, Joost J

Oncoimmunology

2014 Volume 3, Page(s) e28247

Abstract: In a mouse model of breast carcinoma, the combination of cyclophosphamide and transforming growth factor β1,2,3 (TGFβ1,2,3)-targeting antibody achieved superior antineoplastic effects. This novel paradigm of synergistic chemoimmunotherapy promises to ... ...

Abstract	In a mouse model of breast carcinoma, the combination of cyclophosphamide and transforming growth factor β1,2,3 (TGFβ1,2,3)-targeting antibody achieved superior antineoplastic effects. This novel paradigm of synergistic chemoimmunotherapy promises to improve the clinical outcome of cancer patients with micrometastases, and thus deserves further investigation.
Language	English
Publishing date	2014-04-16
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2645309-5
ISSN	2162-402X ; 2162-4011
ISSN (online)	2162-402X
ISSN	2162-4011
DOI	10.4161/onci.28247
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Article ; Online: Transforming growth factor-(beta)s and mammary gland involution; functional roles and implications for cancer progression.

Flanders, Kathleen C / Wakefield, Lalage M

Journal of mammary gland biology and neoplasia

2009 Volume 14, Issue 2, Page(s) 131–144

Abstract: During rodent mammary gland involution there is a dramatic increase in the expression of the transforming growth factor-beta isoform, TGF-beta3. The TGF-betas are multifunctional cytokines which play important roles in wound healing and in carcinogenesis. ...

Abstract	During rodent mammary gland involution there is a dramatic increase in the expression of the transforming growth factor-beta isoform, TGF-beta3. The TGF-betas are multifunctional cytokines which play important roles in wound healing and in carcinogenesis. The responses that are activated in the remodeling of the gland during involution have many similarities with the wound healing process and have been postulated to generate a mammary stroma that provides a microenvironment favoring tumor progression. In this review we will discuss the putative role of TGF-beta during involution, as well as its effects on the mammary microenvironment and possible implications for pregnancy-associated tumorigenesis.
MeSH term(s)	Animals ; Apoptosis/physiology ; Breast Neoplasms/genetics ; Breast Neoplasms/pathology ; Cicatrix/physiopathology ; Disease Progression ; Female ; Gene Expression Profiling ; Humans ; Inflammation/physiopathology ; Lactation/physiology ; Mammary Glands, Animal/physiology ; Mice ; Parity ; Pregnancy ; Pregnancy Complications, Neoplastic/physiopathology ; Prognosis ; Protein Isoforms/physiology ; RNA, Messenger/biosynthesis ; RNA, Neoplasm/biosynthesis ; Transforming Growth Factor beta/genetics ; Transforming Growth Factor beta/physiology ; Transforming Growth Factor beta3/physiology ; Treatment Outcome ; Wound Healing/physiology
Chemical Substances	Protein Isoforms ; RNA, Messenger ; RNA, Neoplasm ; Transforming Growth Factor beta ; Transforming Growth Factor beta3
Language	English
Publishing date	2009-04-25
Publishing country	United States
Document type	Journal Article
ZDB-ID	1327345-0
ISSN	1573-7039 ; 1083-3021
ISSN (online)	1573-7039
ISSN	1083-3021
DOI	10.1007/s10911-009-9122-z
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Zs.A 4478: Show issues

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Article: Keeping order in the neighborhood: new roles for TGFbeta in maintaining epithelial homeostasis.

Wakefield, Lalage M / Stuelten, Christina

Cancer cell

2007 Volume 12, Issue 4, Page(s) 293–295

Abstract: TGFbetas are thought to have tumor suppressor activity in many organ systems, but receptor inactivation in mouse models has not previously resulted in increased spontaneous tumorigenesis. A study in this issue of Cancer Cell shows that mice with a ... ...

Abstract	TGFbetas are thought to have tumor suppressor activity in many organ systems, but receptor inactivation in mouse models has not previously resulted in increased spontaneous tumorigenesis. A study in this issue of Cancer Cell shows that mice with a targeted knockout of the type II TGFbeta receptor in stratified epithelia specifically develop spontaneous squamous cell carcinomas in the anogenital region, but not in the skin. Loss of TGFbeta signaling appears to destabilize the epithelium such that homeostasis fails in the face of persistent proliferative challenge, a normal feature of the anogenital site, and latent invasive and migratory phenotypes are unmasked.
MeSH term(s)	Animals ; Anus Neoplasms/metabolism ; Anus Neoplasms/pathology ; Apoptosis ; Carcinoma, Squamous Cell/enzymology ; Carcinoma, Squamous Cell/genetics ; Carcinoma, Squamous Cell/metabolism ; Carcinoma, Squamous Cell/pathology ; Cell Movement ; Cell Proliferation ; Cell Transformation, Neoplastic/genetics ; Cell Transformation, Neoplastic/metabolism ; Cell Transformation, Neoplastic/pathology ; Epithelial Cells/metabolism ; Epithelial Cells/pathology ; Extracellular Matrix/metabolism ; Focal Adhesion Protein-Tyrosine Kinases/metabolism ; Homeostasis ; Humans ; Integrins/metabolism ; Keratin-14/genetics ; Keratinocytes/metabolism ; Keratinocytes/pathology ; Mice ; Mice, Knockout ; Mutation ; Neoplasm Invasiveness ; Papilloma/metabolism ; Papilloma/pathology ; Promoter Regions, Genetic ; Protein-Serine-Threonine Kinases/deficiency ; Protein-Serine-Threonine Kinases/genetics ; Protein-Serine-Threonine Kinases/metabolism ; Receptors, Transforming Growth Factor beta/deficiency ; Receptors, Transforming Growth Factor beta/genetics ; Receptors, Transforming Growth Factor beta/metabolism ; Signal Transduction ; Skin/metabolism ; Skin/pathology ; Skin/physiopathology ; Skin Neoplasms/metabolism ; Skin Neoplasms/pathology ; Time Factors ; Transforming Growth Factor beta/metabolism ; Urogenital Neoplasms/metabolism ; Urogenital Neoplasms/pathology ; Wound Healing ; ras Proteins/genetics ; ras Proteins/metabolism ; src-Family Kinases/metabolism
Chemical Substances	Integrins ; KRT14 protein, human ; Keratin-14 ; Receptors, Transforming Growth Factor beta ; Transforming Growth Factor beta ; Focal Adhesion Protein-Tyrosine Kinases (EC 2.7.10.2) ; src-Family Kinases (EC 2.7.10.2) ; Protein-Serine-Threonine Kinases (EC 2.7.11.1) ; transforming growth factor-beta type II receptor (EC 2.7.11.30) ; ras Proteins (EC 3.6.5.2)
Language	English
Publishing date	2007-10
Publishing country	United States
Document type	Comment ; Journal Article
ZDB-ID	2078448-X
ISSN	1878-3686 ; 1535-6108
ISSN (online)	1878-3686
ISSN	1535-6108
DOI	10.1016/j.ccr.2007.10.002
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Zs.A 5650: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article: Transforming Growth Factor-βs and Mammary Gland Involution; Functional Roles and Implications for Cancer Progression

Flanders, Kathleen C / Wakefield, Lalage M

Journal of mammary gland biology and neoplasia. 2009 June, v. 14, no. 2

2009

Abstract: During rodent mammary gland involution there is a dramatic increase in the expression of the transforming growth factor-β isoform, TGF-β3. The TGF-βs are multifunctional cytokines which play important roles in wound healing and in carcinogenesis. The ... ...

Abstract	During rodent mammary gland involution there is a dramatic increase in the expression of the transforming growth factor-β isoform, TGF-β3. The TGF-βs are multifunctional cytokines which play important roles in wound healing and in carcinogenesis. The responses that are activated in the remodeling of the gland during involution have many similarities with the wound healing process and have been postulated to generate a mammary stroma that provides a microenvironment favoring tumor progression. In this review we will discuss the putative role of TGF-β during involution, as well as its effects on the mammary microenvironment and possible implications for pregnancy-associated tumorigenesis.
Language	English
Dates of publication	2009-06
Size	p. 131-144.
Publisher	Springer US
Publishing place	Boston
Document type	Article
ZDB-ID	1327345-0
ISSN	1083-3021
ISSN	1083-3021
DOI	10.1007/s10911-009-9122-z
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Regulation of tumor immune surveillance and tumor immune subversion by tgf-Beta.

Park, Hae-Young / Wakefield, Lalage M / Mamura, Mizuko

Immune network

2009 Volume 9, Issue 4, Page(s) 122–126

Abstract: Transforming growth factor-beta (TGF-beta) is a highly pleiotropic cytokine playing pivotal roles in immune regulation. TGF-beta facilitates tumor cell survival and metastasis by targeting multiple cellular components. Focusing on its immunosuppressive ... ...

Abstract	Transforming growth factor-beta (TGF-beta) is a highly pleiotropic cytokine playing pivotal roles in immune regulation. TGF-beta facilitates tumor cell survival and metastasis by targeting multiple cellular components. Focusing on its immunosuppressive functions, TGF-beta antagonists have been employed for cancer treatment to enhance tumor immunity. TGF-beta antagonists exert anti-tumor effects through #1 activating effector cells such as NK cells and cytotoxic CD8(+) T cells (CTLs), #2 inhibiting regulatory/suppressor cell populations, #3 making tumor cells visible to immune cells, #4 inhibiting the production of tumor growth factors. This review focuses on the effect of TGF-beta on T cells, which are differentiated into effector T cells or newly identified tumor-supporting T cells.
Language	English
Publishing date	2009-08-31
Publishing country	Korea (South)
Document type	Journal Article
ZDB-ID	2536191-0
ISSN	2092-6685 ; 2092-6685
ISSN (online)	2092-6685
ISSN	2092-6685
DOI	10.4110/in.2009.9.4.122
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Article ; Online: Quantitation of TGF-β proteins in mouse tissues shows reciprocal changes in TGF-β1 and TGF-β3 in normal vs neoplastic mammary epithelium.

Flanders, Kathleen C / Yang, Yu-An / Herrmann, Michelle / Chen, JinQiu / Mendoza, Nerissa / Mirza, Amer M / Wakefield, Lalage M

Oncotarget

2016 Volume 7, Issue 25, Page(s) 38164–38179

Abstract: Transforming growth factor-βs (TGF-βs) regulate tissue homeostasis, and their expression is perturbed in many diseases. The three isoforms (TGF-β1, -β2, and -β3) have similar bioactivities in vitro but show distinct activities in vivo. Little ... ...

Abstract	Transforming growth factor-βs (TGF-βs) regulate tissue homeostasis, and their expression is perturbed in many diseases. The three isoforms (TGF-β1, -β2, and -β3) have similar bioactivities in vitro but show distinct activities in vivo. Little quantitative information exists for expression of TGF-β isoform proteins in physiology or disease. We developed an optimized method to quantitate protein levels of the three isoforms, using a Luminex® xMAP®-based multianalyte assay following acid-ethanol extraction of tissues. Analysis of multiple tissues and plasma from four strains of adult mice showed that TGF-β1 is the predominant isoform with TGF-β2 being ~10-fold lower. There were no sex-specific differences in isoform expression, but some tissues showed inter-strain variation, particularly for TGF-β2. The only adult tissue expressing appreciable TGF-β3 was the mammary gland, where its levels were comparable to TGF-β1. In situ hybridization showed the luminal epithelium as the major source of all TGF-β isoforms in the normal mammary gland. TGF-β1 protein was 3-8-fold higher in three murine mammary tumor models than in normal mammary gland, while TGF-β3 protein was 2-3-fold lower in tumors than normal tissue, suggesting reciprocal regulation of these isoforms in mammary tumorigenesis.
MeSH term(s)	Animals ; Female ; Humans ; Mammary Neoplasms, Experimental/immunology ; Mammary Neoplasms, Experimental/pathology ; Mice ; Mice, Inbred BALB C ; Protein Isoforms ; Transforming Growth Factor beta/metabolism ; Transforming Growth Factor beta1/metabolism ; Transforming Growth Factor beta3/metabolism
Chemical Substances	Protein Isoforms ; Transforming Growth Factor beta ; Transforming Growth Factor beta1 ; Transforming Growth Factor beta3
Language	English
Publishing date	2016-05-19
Publishing country	United States
Document type	Journal Article
ZDB-ID	2560162-3
ISSN	1949-2553 ; 1949-2553
ISSN (online)	1949-2553
ISSN	1949-2553
DOI	10.18632/oncotarget.9416
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Article: The two faces of transforming growth factor beta in carcinogenesis.

Roberts, Anita B / Wakefield, Lalage M

Proceedings of the National Academy of Sciences of the United States of America

2003 Volume 100, Issue 15, Page(s) 8621–8623

MeSH term(s)	Animals ; Female ; Genes, Tumor Suppressor ; Humans ; Mammary Neoplasms, Experimental/etiology ; Mammary Neoplasms, Experimental/genetics ; Mammary Neoplasms, Experimental/physiopathology ; Mice ; Models, Biological ; Neoplasm Metastasis/genetics ; Neoplasm Metastasis/physiopathology ; Neoplasm Metastasis/therapy ; Neoplasms/etiology ; Neoplasms/genetics ; Neoplasms/physiopathology ; Oncogenes ; Signal Transduction ; Transforming Growth Factor beta/physiology ; Tumor Suppressor Proteins/physiology
Chemical Substances	Transforming Growth Factor beta ; Tumor Suppressor Proteins
Language	English
Publishing date	2003-07-22
Publishing country	United States
Document type	Comment ; Journal Article ; Review
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.1633291100
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