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Article ; Online: SLC1A5 co-expression with TALDO1 associates with endocrine therapy failure in estrogen receptor-positive breast cancer.

Alfarsi, Lutfi H / El Ansari, Rokaya / Craze, Madeleine L / Mohammed, Omar J / Masisi, Brendah K / Ellis, Ian O / Rakha, Emad A / Green, Andrew R

Breast cancer research and treatment

2021 Volume 189, Issue 2, Page(s) 317–331

Abstract: Purpose: Identification of effective biomarkers for the benefit of endocrine treatment and understanding the molecular pathways that contribute to the development of resistance are of crucial importance to the management of luminal breast cancer. The ... ...

Abstract	Purpose: Identification of effective biomarkers for the benefit of endocrine treatment and understanding the molecular pathways that contribute to the development of resistance are of crucial importance to the management of luminal breast cancer. The amino acid transporter SLC1A5 has emerging importance as a prognostic marker and potential therapeutic target in various types of cancer. This study aims to investigate its role in luminal breast cancer as a potential predictive marker for endocrine treatment. Methods: SLC1A5 expression was assessed at the transcriptomic and proteomic levels in large, well-characterized cohorts of luminal breast cancer. The sensitivity to endocrine therapy after SLC1A5 knockdown was investigated in vitro, using MCF7 and MDA-MB-175 cell lines. Bioinformatic analyses were performed to study the interacting networks of SLC1A5 and to identify a key co-expressed gene with SLC1A5. Results: Here, we showed that patients with tumors that highly expressed SLC1A5 associated with a high risk of relapse after endocrine treatment. In vitro, depletion of SLC1A5 increases the sensitivity of luminal breast cancer cells to tamoxifen. TALDO1 was identified as key co-expressed gene with SLC1A5, and in vitro knockdown of SLC1A5 showed reduction in TALDO1 expression. Indeed, TALDO1 was associated with poor clinical outcomes in patients who were subject to endocrine therapy. Conclusion: These findings suggest that metabolic alterations, particularly the interaction between the key amino acid transporter SLC1A5 and metabolic enzyme TALDO1, could affect the sensitivity of endocrine therapy. This study demonstrated the prognostic value of both SLC1A5 and TALDO1 as biomarkers in luminal breast cancer.
MeSH term(s)	Amino Acid Transport System ASC/genetics ; Antineoplastic Agents, Hormonal/pharmacology ; Antineoplastic Agents, Hormonal/therapeutic use ; Breast Neoplasms/drug therapy ; Breast Neoplasms/genetics ; Cell Line, Tumor ; Drug Resistance, Neoplasm/genetics ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Minor Histocompatibility Antigens/genetics ; Neoplasm Recurrence, Local ; Proteomics ; Receptors, Estrogen/genetics ; Receptors, Estrogen/metabolism ; Tamoxifen/therapeutic use ; Transaldolase/genetics
Chemical Substances	Amino Acid Transport System ASC ; Antineoplastic Agents, Hormonal ; Minor Histocompatibility Antigens ; Receptors, Estrogen ; SLC1A5 protein, human ; Tamoxifen (094ZI81Y45) ; Transaldolase (EC 2.2.1.2)
Language	English
Publishing date	2021-07-19
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	604563-7
ISSN	1573-7217 ; 0167-6806
ISSN (online)	1573-7217
ISSN	0167-6806
DOI	10.1007/s10549-021-06298-1
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Article ; Online: A PSTOL-like gene, TaPSTOL, controls a number of agronomically important traits in wheat.

Milner, Matthew J / Howells, Rhian M / Craze, Melanie / Bowden, Sarah / Graham, Neil / Wallington, Emma J

BMC plant biology

2018 Volume 18, Issue 1, Page(s) 115

Abstract: ... desirable to both breeders and farmers. Here, we clone the wheat (Triticum aestivum L.) homologue ...

Abstract	Background: Phosphorus (P) is an essential macronutrient for plant growth, and is required in large quantities by elite varieties of crops to maintain yields. Approximately 70% of global cultivated land suffers from P deficiency, and it has recently been estimated that worldwide P resources will be exhausted by the end of this century, increasing the demand for crops more efficient in their P usage. A greater understanding of how plants are able to maintain yield with lower P inputs is, therefore, highly desirable to both breeders and farmers. Here, we clone the wheat (Triticum aestivum L.) homologue of the rice PSTOL gene (OsPSTOL), and characterize its role in phosphate nutrition plus other agronomically important traits. Results: TaPSTOL is a single copy gene located on the short arm of chromosome 5A, encoding a putative kinase protein, and shares a high level of sequence similarity to OsPSTOL. We re-sequenced TaPSTOL from 24 different wheat accessions and (3) three T. durum varieties. No sequence differences were detected in 26 of the accessions, whereas two indels were identified in the promoter region of one of the durum wheats. We characterised the expression of TaPSTOL under different P concentrations and demonstrated that the promoter was induced in root tips and hairs under P limiting conditions. Overexpression and RNAi silencing of TaPSTOL in transgenic wheat lines showed that there was a significant effect upon root biomass, flowering time independent of P treatment, tiller number and seed yield, correlating with the expression of TaPSTOL. However this did not increase PUE as elevated P concentration in the grain did not correspond to increased yields. Conclusions: Manipulation of TaPSTOL expression in wheat shows it is responsible for many of the previously described phenotypic advantages as OsPSTOL except yield. Furthermore, we show TaPSTOL contributes to additional agronomically important traits including flowering time and grain size. Analysis of TaPSTOL sequences from a broad selection of wheat varieties, encompassing 91% of the genetic diversity in UK bread wheat, showed that there is very little genetic variation in this gene, which would suggest that this locus may have been under high selection pressure.
MeSH term(s)	Edible Grain/growth & development ; Edible Grain/metabolism ; Flowers/growth & development ; Flowers/metabolism ; Genes, Plant/genetics ; Genes, Plant/physiology ; Phosphates/metabolism ; Quantitative Trait, Heritable ; Sequence Analysis, DNA ; Triticum/genetics ; Triticum/growth & development
Chemical Substances	Phosphates
Language	English
Publishing date	2018-06-08
Publishing country	England
Document type	Journal Article
ZDB-ID	2059868-3
ISSN	1471-2229 ; 1471-2229
ISSN (online)	1471-2229
ISSN	1471-2229
DOI	10.1186/s12870-018-1331-4
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Article ; Online: Co-Expression Effect of SLC7A5/SLC3A2 to Predict Response to Endocrine Therapy in Oestrogen-Receptor-Positive Breast Cancer.

Alfarsi, Lutfi H / El-Ansari, Rokaya / Craze, Madeleine L / Masisi, Brendah K / Mohammed, Omar J / Ellis, Ian O / Rakha, Emad A / Green, Andrew R

International journal of molecular sciences

2020 Volume 21, Issue 4

Abstract: The majority of breast cancers are oestrogen-receptor-positive (ER+) and are subject to endocrine therapy; however, an unpredictable subgroup of patients will develop resistance to endocrine therapy. The SLC7A5/SLC3A2 complex is a major route for the ... ...

Abstract	The majority of breast cancers are oestrogen-receptor-positive (ER+) and are subject to endocrine therapy; however, an unpredictable subgroup of patients will develop resistance to endocrine therapy. The SLC7A5/SLC3A2 complex is a major route for the transport of large neutral essential amino acids through the plasma membrane. Alterations in the expression and function of those amino-acid transporters lead to metabolic reprogramming, which contributes to the tumorigenesis and drug resistance. This study aims to assess the effects and roles of SLC7A5/SLC3A2 co-expression in predicting responses to endocrine therapy in patients with ER+ breast cancer. The biological and clinical impact of SLC7A5/SLC3A2 co-expression was assessed in large annotated cohorts of ER+/HER2- breast cancer with long-term follow-up at the mRNA and protein levels. In vitro experiments were conducted to investigate the effect of SLC7A5/SLC3A2 knockdown in the proliferation of cancer cells and to the sensitivity to tamoxifen. We found that proliferation-related genes are highly expressed in a subgroup of patients with high SLC7A5/SLC3A2, and knockdown of SLC7A5/SLC3A2 decreased proliferation of ER+ breast cancer cells. In patients treated with endocrine therapy, high SLC7A5/SLC3A2 co-expression was associated with poor patient outcome, and depletion of SLC7A5/SLC3A2 using siRNA increased the sensitivity of breast cancer cells to tamoxifen. On the basis of our findings, SLC7A5/SLC3A2 co-expression has the potential of identifying a subgroup of ER+/HER2- breast cancer patients who fail to benefit from endocrine therapy and could guide the choice of other alternative therapies.
MeSH term(s)	Antineoplastic Agents, Hormonal/therapeutic use ; Biomarkers, Tumor/genetics ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/drug therapy ; Breast Neoplasms/genetics ; Breast Neoplasms/metabolism ; Breast Neoplasms/pathology ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Cell Proliferation/genetics ; Cohort Studies ; Drug Resistance, Neoplasm/genetics ; Female ; Fusion Regulatory Protein 1, Heavy Chain/genetics ; Fusion Regulatory Protein 1, Heavy Chain/metabolism ; Gene Expression Regulation, Neoplastic/drug effects ; Gene Expression Regulation, Neoplastic/genetics ; Gene Knockdown Techniques ; Humans ; Kaplan-Meier Estimate ; Large Neutral Amino Acid-Transporter 1/genetics ; Large Neutral Amino Acid-Transporter 1/metabolism ; Middle Aged ; Neoplasm Metastasis/genetics ; Prognosis ; RNA, Small Interfering ; Receptors, Estrogen/metabolism ; Regression Analysis ; Tamoxifen/pharmacology ; Tamoxifen/therapeutic use
Chemical Substances	Antineoplastic Agents, Hormonal ; Biomarkers, Tumor ; Fusion Regulatory Protein 1, Heavy Chain ; Large Neutral Amino Acid-Transporter 1 ; RNA, Small Interfering ; Receptors, Estrogen ; SLC3A2 protein, human ; SLC7A5 protein, human ; Tamoxifen (094ZI81Y45)
Language	English
Publishing date	2020-02-19
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms21041407
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Article: Identification of genes involved in male sterility in wheat (Triticum aestivum L.) which could be used in a genic hybrid breeding system

Milner, Matthew J. / Craze, Melanie / Bowden, Sarah / Bates, Ruth / Wallington, Emma J. / Keeling, Anthony

Plant direct. 2020 Mar., v. 4, no. 3

2020

Abstract: Wheat is grown on more land than any other crop in the world. Current estimates suggest that yields will have to increase sixty percent by 2050 to meet the demand of an ever‐increasing human population; however, recent wheat yield gains have lagged ... ...

Abstract	Wheat is grown on more land than any other crop in the world. Current estimates suggest that yields will have to increase sixty percent by 2050 to meet the demand of an ever‐increasing human population; however, recent wheat yield gains have lagged behind other major crops such as rice and maize. One of the reasons suggested for the lag in yield potential is the lack of a robust hybrid system to harness the potential yield gains associated with heterosis, also known as hybrid vigor. Here, we set out to identify candidate genes for a genic hybrid system in wheat and characterize their function in wheat using RNASeq on stamens and carpels undergoing meiosis. Twelve genes were identified as potentially playing a role in pollen viability. CalS5‐ and RPG1‐like genes were identified as pre‐ and post‐meiotic genes for further characterization and to determine their role in pollen viability. It appears that all three homoeologues of both CalS5 and RPG1 are functional in wheat as all three homoeologues need to be knocked out in order to cause male sterility. However, one functional homoeologue is sufficient to maintain male fertility in wheat.
Keywords	Triticum aestivum ; corn ; heterosis ; human population ; hybrids ; male fertility ; male sterility ; meiosis ; pollen viability ; rice ; wheat
Language	English
Dates of publication	2020-03
Publishing place	John Wiley & Sons, Ltd
Document type	Article
Note	JOURNAL ARTICLE
ISSN	2475-4455
DOI	10.1002/pld3.201
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: A mixed-spin spin-crossover thiozolylimine [Fe

Li, Li / Craze, Alexander R / Mustonen, Outi / Zenno, Hikaru / Whittaker, Jacob J / Hayami, Shinya / Lindoy, Leonard F / Marjo, Christopher E / Clegg, Jack K / Aldrich-Wright, Janice R / Li, Feng

Dalton transactions (Cambridge, England : 2003)

2019 Volume 48, Issue 27, Page(s) 9935–9938

Abstract: The self-assembly of a mixed-spin [ ... ...

Abstract	The self-assembly of a mixed-spin [Fe
Language	English
Publishing date	2019-06-14
Publishing country	England
Document type	Journal Article
ZDB-ID	1472887-4
ISSN	1477-9234 ; 1364-5447 ; 0300-9246 ; 1477-9226
ISSN (online)	1477-9234 ; 1364-5447
ISSN	0300-9246 ; 1477-9226
DOI	10.1039/c9dt01947b
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Article ; Online: Co-Expression Effect of SLC7A5/SLC3A2 to Predict Response to Endocrine Therapy in Oestrogen-Receptor-Positive Breast Cancer

Lutfi H. Alfarsi / Rokaya El-Ansari / Madeleine L. Craze / Brendah K. Masisi / Omar J. Mohammed / Ian O. Ellis / Emad A. Rakha / Andrew R. Green

International Journal of Molecular Sciences, Vol 21, Iss 4, p

2020 Volume 1407

Abstract	The majority of breast cancers are oestrogen-receptor-positive (ER+) and are subject to endocrine therapy; however, an unpredictable subgroup of patients will develop resistance to endocrine therapy. The SLC7A5/SLC3A2 complex is a major route for the transport of large neutral essential amino acids through the plasma membrane. Alterations in the expression and function of those amino-acid transporters lead to metabolic reprogramming, which contributes to the tumorigenesis and drug resistance. This study aims to assess the effects and roles of SLC7A5/SLC3A2 co-expression in predicting responses to endocrine therapy in patients with ER+ breast cancer. The biological and clinical impact of SLC7A5/SLC3A2 co-expression was assessed in large annotated cohorts of ER+/HER2− breast cancer with long-term follow-up at the mRNA and protein levels. In vitro experiments were conducted to investigate the effect of SLC7A5/SLC3A2 knockdown in the proliferation of cancer cells and to the sensitivity to tamoxifen. We found that proliferation-related genes are highly expressed in a subgroup of patients with high SLC7A5/SLC3A2, and knockdown of SLC7A5/SLC3A2 decreased proliferation of ER+ breast cancer cells. In patients treated with endocrine therapy, high SLC7A5/SLC3A2 co-expression was associated with poor patient outcome, and depletion of SLC7A5/SLC3A2 using siRNA increased the sensitivity of breast cancer cells to tamoxifen. On the basis of our findings, SLC7A5/SLC3A2 co-expression has the potential of identifying a subgroup of ER+/HER2− breast cancer patients who fail to benefit from endocrine therapy and could guide the choice of other alternative therapies.
Keywords	breast cancer ; oestrogen receptor ; endocrine resistance ; slc7a5 ; slc3a2 ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	610 ; 616
Language	English
Publishing date	2020-02-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Arabidopsis EF-Tu receptor enhances bacterial disease resistance in transgenic wheat.

Schoonbeek, Henk-Jan / Wang, Hsi-Hua / Stefanato, Francesca L / Craze, Melanie / Bowden, Sarah / Wallington, Emma / Zipfel, Cyril / Ridout, Christopher J

The New phytologist

2015 Volume 206, Issue 2, Page(s) 606–613

Abstract: Perception of pathogen (or microbe)-associated molecular patterns (PAMPs/MAMPs) by pattern recognition receptors (PRRs) is a key component of plant innate immunity. The Arabidopsis PRR EF-Tu receptor (EFR) recognizes the bacterial PAMP elongation factor ... ...

Abstract	Perception of pathogen (or microbe)-associated molecular patterns (PAMPs/MAMPs) by pattern recognition receptors (PRRs) is a key component of plant innate immunity. The Arabidopsis PRR EF-Tu receptor (EFR) recognizes the bacterial PAMP elongation factor Tu (EF-Tu) and its derived peptide elf18. Previous work revealed that transgenic expression of AtEFR in Solanaceae confers elf18 responsiveness and broad-spectrum bacterial disease resistance. In this study, we developed a set of bioassays to study the activation of PAMP-triggered immunity (PTI) in wheat. We generated transgenic wheat (Triticum aestivum) plants expressing AtEFR driven by the constitutive rice actin promoter and tested their response to elf18. We show that transgenic expression of AtEFR in wheat confers recognition of elf18, as measured by the induction of immune marker genes and callose deposition. When challenged with the cereal bacterial pathogen Pseudomonas syringae pv. oryzae, transgenic EFR wheat lines had reduced lesion size and bacterial multiplication. These results demonstrate that AtEFR can be transferred successfully from dicot to monocot species, further revealing that immune signalling pathways are conserved across these distant phyla. As novel PRRs are identified, their transfer between plant families represents a useful strategy for enhancing resistance to pathogens in crops.
MeSH term(s)	Arabidopsis/genetics ; Arabidopsis Proteins/genetics ; Arabidopsis Proteins/metabolism ; Bacterial Proteins/genetics ; Bacterial Proteins/metabolism ; Biological Assay ; Disease Resistance ; Gene Expression Regulation, Plant ; Glucans/metabolism ; Oryza/genetics ; Peptide Elongation Factor Tu/genetics ; Peptide Elongation Factor Tu/metabolism ; Plant Diseases/immunology ; Plant Diseases/microbiology ; Plants, Genetically Modified ; Pseudomonas syringae/physiology ; Receptors, Pattern Recognition/genetics ; Receptors, Pattern Recognition/metabolism ; Signal Transduction ; Triticum/genetics ; Triticum/immunology ; Triticum/microbiology
Chemical Substances	Arabidopsis Proteins ; Bacterial Proteins ; EFR protein, Arabidopsis ; Glucans ; Receptors, Pattern Recognition ; callose (9064-51-1) ; Peptide Elongation Factor Tu (EC 3.6.1.-)
Language	English
Publishing date	2015-03-11
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	208885-x
ISSN	1469-8137 ; 0028-646X
ISSN (online)	1469-8137
ISSN	0028-646X
DOI	10.1111/nph.13356
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Article ; Online: Self-Assembly of a Rare High Spin Fe II /Pd II Tetradecanuclear Cubic Cage Constructed via the Metalloligand Approach

Hyunsung Min / Alexander R. Craze / Takahiro Taira / Matthew J. Wallis / Mohan M. Bhadbhade / Ruoming Tian / Daniel J. Fanna / Richard Wuhrer / Shinya Hayami / Jack K. Clegg / Christopher E. Marjo / Leonard F. Lindoy / Feng Li

Chemistry, Vol 4, Iss 38, Pp 535-

2022 Volume 547

Abstract: ... we present the synthesis and characterisation of a new tetradecanuclear heterobimetallic [Fe 8 Pd 6 L 8 ](BF ...

Abstract	Polynuclear heterobimetallic coordination cages in which different metal cations are connected within a ligand scaffold are known to adopt a variety of polyhedral architectures, many of which display interesting functions. Within the extensive array of coordination cages incorporating Fe(II) centres reported so far, the majority contain low-spin (LS) Fe(II), with high-spin (HS) Fe(II) being less common. Herein, we present the synthesis and characterisation of a new tetradecanuclear heterobimetallic [Fe 8 Pd 6 L 8 ](BF 4 ] 28 ( 1 ) cubic cage utilising the metalloligand approach. Use of the tripodal tris-imidazolimine derivative ( 2 ) permitted the formation of the tripodal HS Fe(II) metalloligand [FeL](BF 4 ) 2 ·CH 3 OH ( 3 ) that was subsequently used to form the coordination cage 1 . Magnetic and structural analyses gave insight into the manner in which the HS environment of the metalloligand was transferred into the cage architecture along with the structural changes that accompanied its occupancy of the eight corners of the discrete cubic structure.
Keywords	cubic cage ; metalloligand ; tripodal ligand ; heterobimetallic ; Chemistry ; QD1-999
Subject code	290
Language	English
Publishing date	2022-05-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
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Article ; Online: Multicomponent analysis of the tumour microenvironment reveals low CD8 T cell number, low stromal caveolin-1 and high tenascin-C and their combination as significant prognostic markers in non-small cell lung cancer.

Onion, David / Isherwood, Mark / Shridhar, Naveen / Xenophontos, Mikalena / Craze, Madeleine L / Day, Laura J / García-Márquez, María A / Pineda, Robert G / Reece-Smith, Alexander M / Saunders, John H / Duffy, John P / Argent, Richard H / Grabowska, Anna M

Oncotarget

2018 Volume 9, Issue 2, Page(s) 1760–1771

Abstract: The complex interplay of the tumour microenvironment (TME) and its role in disease progression and response to therapy is poorly understood. The majority of studies to date focus on individual components or molecules within the TME and so lack the power ... ...

Abstract	The complex interplay of the tumour microenvironment (TME) and its role in disease progression and response to therapy is poorly understood. The majority of studies to date focus on individual components or molecules within the TME and so lack the power correlative analysis. Here we have performed a multi-parameter analysis of the TME in 62 resectable non-small cell lung cancer (NSCLC) specimens detailing number and location of immune infiltrate, assessing markers of cancer-associated fibroblasts, caveolin-1 and tenascin-C, and correlating with clinicopathological details, as well as markers of disease progression such as epithelial-to-mesenchymal transition (EMT). The influence of individual parameters on overall survival was determined in univariate and multivariate analysis and the combination of risk factors and interplay between components analysed. Low numbers of CD8 T cells, low stromal levels of caveolin-1 or high levels of tenascin-C were significant prognostic markers of decreased overall survival in both univariate and multivariate analysis. Patients with two or more risk factors had dramatically reduced overall survival and those with all three a median survival of just 7.5 months. In addition, low levels of tumour E-cadherin correlated with reduced immune infiltrate into the tumour nests, possibly linking EMT to the avoidance of CD8 T cell control. The multicomponent approach has allowed identification of the dominant influences on overall survival, and exploration of the interplay between different components of the TME in NSCLC.
Language	English
Publishing date	2018-01-05
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.18880
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Article: Langerhans' cell histiocytosis: a case history.

Craze, J L / Pritchard, J

Annals of oncology : official journal of the European Society for Medical Oncology

1996 Volume 7, Issue 1, Page(s) 89–94

MeSH term(s)	Adult ; Histiocytosis, Langerhans-Cell/therapy ; Humans ; Male ; Prognosis
Language	English
Publishing date	1996-01
Publishing country	England
Document type	Case Reports ; Journal Article ; Review
ZDB-ID	1025984-3
ISSN	1569-8041 ; 0923-7534
ISSN (online)	1569-8041
ISSN	0923-7534
DOI	10.1093/oxfordjournals.annonc.a010487
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