Advertisement

The Eleventh ENBDC Workshop: Advances in Technology Help to Unveil Mechanisms of Mammary Gland Development and Cancerogenesis

  • Vida Vafaizadeh
  • Emilia Peuhu
  • Marja L. Mikkola
  • Walid T. Khaled
  • Mohamed Bentires-Alj
  • Zuzana KoledovaEmail author
Article

Abstract

The eleventh annual workshop of the European Network for Breast Development and Cancer, Methods in mammary gland biology and breast cancer, took place on the 16th to 18th of May 2019 in Weggis, Switzerland. The main topics of the meeting were high resolution genomics and proteomics for the study of mammary gland development and cancer, breast cancer signaling, tumor microenvironment, preclinical models of breast cancer, and tissue morphogenesis. Exciting novel findings in, or highly relevant to, mammary gland biology and breast cancer field were presented, with insights into the methods used to obtain them. Among others, the discussed methods included single-cell RNA sequencing, genetic barcoding, lineage tracing, spatial transcriptomics, optogenetics, genetic mouse models and organoids.

Keywords

Barcoding Proteomics Signaling Tissue morphogenesis Transcriptomics Tumor microenvironment 

Abbreviations

53BP1

p53-binding protein 1

BRCA1

BRCA1 DNA repair associated

cAMP

cyclic adenosine monophosphate

CAF

cancer-associated fibroblast

CDC42EP3

cell division cycle 42 effector protein 3

CREB1

cAMP responsive element binding protein 1

EGFR

epithelial growth factor receptor

ECM

extracellular matrix

EMBL

European Molecular Biology Laboratory

ENBDC

European Network of Breast Development and Cancer

ER

estrogen receptor

FGF

fibroblast growth factor

FGFR

fibroblast growth factor receptor

IDC

invasive ductal carcinoma

MSPC

mammary stem/progenitor cell

NOTCH4

notch receptor 4

PARP

poly (ADP-ribose) polymerase

PARPi

PARP inhibitor

PR

progesterone receptor

RSK2

p90 ribosomal S6 kinase 2

scRNAseq

single cell RNA sequencing

TNBC

triple negative breast cancer

UK

United Kingdom

VPS11

vacuolar protein sorting-associated protein 11 homolog

YAP

Yes-associated protein

Notes

Acknowledgements

The authors thank Xiomara Banholzer for help with the organization of the meeting.

Authors’ Contributions

VV, EP, MLM, WTK, MB-A, and ZK wrote the manuscript. All authors approved the final manuscript.

Funding Information

Funding for the meeting was received from Krebsforschung Schweiz and Krebsliga Schweiz, Novartis, The Company of Biologists, Frontiers in Cell and Developmental Biology, Cytoskeleton Inc., and from European Association for Cancer Research. VV has been supported by the Swiss National Science Foundation, EP has been supported by Academy of Finland and Finnish Cultural foundation. MLM received funding from Academy of Finland, Cancer Foundation Finland, and Sigrid Juselius Foundation. Research in the MB-A laboratory is supported by the Swiss Initiative for Systems Biology- SystemsX, the European Research Council (grant no. 694033 STEM-BCPC), the Swiss National Science Foundation, Novartis, the Krebsliga Beider Basel, the Swiss Cancer League, the Swiss Personalized Health Network (Swiss Personalized Oncology driver project) and the Department of Surgery of the University Hospital Basel. ZK is supported by the Grant Agency of Masaryk University (grants no. MUNI/G/1446/2018 and MUNI/E/0519/2019).

Compliance with Ethical Standards

Ethics Approval and Consent to Participate

Not applicable.

Consent for Publication

The manuscript has been read and approved by all authors, has not been published previously in print or electronic format, and is not under consideration by another publication or electronic medium. Consent for publication has been obtained from all the speakers.

Conflict of Interest

The authors declare that they have no conflict of interest.

References

  1. 1.
    Pal B, Chen Y, Vaillant F, Jamieson P, Gordon L, Rios AC, et al. Construction of developmental lineage relationships in the mouse mammary gland by single-cell RNA profiling. Nat Commun. 2017;8:1627.CrossRefGoogle Scholar
  2. 2.
    Merino D, Weber TS, Serrano A, Vaillant F, Liu K, Pal B, et al. Barcoding reveals complex clonal behavior in patient-derived xenografts of metastatic triple negative breast cancer. Nat Commun. 2019;10:766.CrossRefGoogle Scholar
  3. 3.
    Ståhl PL, Salmén F, Vickovic S, Lundmark A, Navarro JF, Magnusson J, et al. Visualization and analysis of gene expression in tissue sections by spatial transcriptomics. Science. 2016;353:78–82.CrossRefGoogle Scholar
  4. 4.
    Salmén F, Vickovic S, Larsson L, Stenbeck L, Vallon-Christersson J, Ehinger A, et al. Multidimensional transcriptomics provides detailed information about immune cell distribution and identity in HER2+ breast tumors. bioRxiv. 2018;358937.Google Scholar
  5. 5.
    Francavilla C, Rigbolt KTG, Emdal KB, Carraro G, Vernet E, Bekker-Jensen DB, et al. Functional proteomics defines the molecular switch underlying FGF receptor trafficking and cellular outputs. Mol Cell. 2013;51:707–22.CrossRefGoogle Scholar
  6. 6.
    Piasecka D, Kitowska K, Czaplinska D, Mieczkowski K, Mieszkowska M, Turczyk L, et al. Fibroblast growth factor signalling induces loss of progesterone receptor in breast cancer cells. Oncotarget. 2016;7:86011–25.CrossRefGoogle Scholar
  7. 7.
    Piasecka D, Braun M, Kitowska K, Mieczkowski K, Kordek R, Sadej R, et al. FGFs/FGFRs-dependent signalling in regulation of steroid hormone receptors - implications for therapy of luminal breast cancer. J Exp Clin Cancer Res CR. 2019;38:230.CrossRefGoogle Scholar
  8. 8.
    Berto M, Jean V, Zwart W, Picard D. ERα activity depends on interaction and target site corecruitment with phosphorylated CREB1. Life Sci Alliance. 2018;1:e201800055.CrossRefGoogle Scholar
  9. 9.
    Segala G, Bennesch MA, Ghahhari NM, Pandey DP, Echeverria PC, Karch F, et al. Vps11 and Vps18 of Vps-C membrane traffic complexes are E3 ubiquitin ligases and fine-tune signalling. Nat Commun. 2019;10:1833.CrossRefGoogle Scholar
  10. 10.
    Gaggioli C, Hooper S, Hidalgo-Carcedo C, Grosse R, Marshall JF, Harrington K, et al. Fibroblast-led collective invasion of carcinoma cells with differing roles for RhoGTPases in leading and following cells. Nat Cell Biol. 2007;9:1392–400.CrossRefGoogle Scholar
  11. 11.
    Calvo F, Ege N, Grande-Garcia A, Hooper S, Jenkins RP, Chaudhry SI, et al. Mechanotransduction and YAP-dependent matrix remodelling is required for the generation and maintenance of cancer-associated fibroblasts. Nat Cell Biol. 2013;15:637–46.CrossRefGoogle Scholar
  12. 12.
    Calvo F, Ranftl R, Hooper S, Farrugia AJ, Moeendarbary E, Bruckbauer A, et al. Cdc42EP3/BORG2 and Septin network enables Mechano-transduction and the emergence of Cancer-associated fibroblasts. Cell Rep. 2015;13:2699–714.CrossRefGoogle Scholar
  13. 13.
    Duarte AA, Gogola E, Sachs N, Barazas M, Annunziato S, R de Ruiter J, et al. BRCA-deficient mouse mammary tumor organoids to study cancer-drug resistance. Nat Methods. 2018;15:134–40.CrossRefGoogle Scholar
  14. 14.
    Gogola E, Duarte AA, de Ruiter JR, Wiegant WW, Schmid JA, de Bruijn R, et al. Selective loss of PARG restores PARylation and counteracts PARP inhibitor-mediated synthetic lethality. Cancer Cell. 2018;33:1078–93 e12.CrossRefGoogle Scholar
  15. 15.
    Noordermeer SM, Adam S, Setiaputra D, Barazas M, Pettitt SJ, Ling AK, et al. The shieldin complex mediates 53BP1-dependent DNA repair. Nature. 2018;560:117–21.CrossRefGoogle Scholar
  16. 16.
    Barazas M, Gasparini A, Huang Y, Küçükosmanoğlu A, Annunziato S, Bouwman P, et al. Radiosensitivity is an acquired vulnerability of PARPi-resistant BRCA1-deficient tumors. Cancer Res. 2019;79:452–60.CrossRefGoogle Scholar
  17. 17.
    Acerbi I, Cassereau L, Dean I, Shi Q, Au A, Park C, et al. Human breast cancer invasion and aggression correlates with ECM stiffening and immune cell infiltration. Integr Biol Quant Biosci Nano Macro. 2015;7:1120–34.Google Scholar
  18. 18.
    Mohammadi H, Sahai E. Mechanisms and impact of altered tumour mechanics. Nat Cell Biol. 2018;20:766–74.CrossRefGoogle Scholar
  19. 19.
    Mayorca-Guiliani AE, Madsen CD, Cox TR, Horton ER, Venning FA, Erler JT. ISDoT: in situ decellularization of tissues for high-resolution imaging and proteomic analysis of native extracellular matrix. Nat Med. 2017;23:890–8.CrossRefGoogle Scholar
  20. 20.
    Northcott JM, Dean IS, Mouw JK, Weaver VM. Feeling stress: the mechanics of Cancer progression and aggression. Front Cell Dev Biol. 2018;6:17.CrossRefGoogle Scholar
  21. 21.
    Simões BM, O’Brien CS, Eyre R, Silva A, Yu L, Sarmiento-Castro A, et al. Anti-estrogen resistance in human breast tumors is driven by JAG1-NOTCH4-dependent Cancer stem cell activity. Cell Rep. 2015;12:1968–77.CrossRefGoogle Scholar
  22. 22.
    Zhao Y, Hu Q, Cheng F, Su N, Wang A, Zou Y, et al. SoNar, a highly responsive NAD+/NADH sensor, allows high-throughput metabolic screening of anti-tumor agents. Cell Metab. 2015;21:777–89.CrossRefGoogle Scholar
  23. 23.
    Nelson CM. On Buckling Morphogenesis. J Biomech Eng. 2016;138:021005.CrossRefGoogle Scholar
  24. 24.
    Pearl EJ, Li J, Green JBA. Cellular systems for epithelial invagination. Philos Trans R Soc B Biol Sci. 2017;372:20150526.CrossRefGoogle Scholar
  25. 25.
    Li J, Economou AD, Green JBA. Epithelial invagination by vertical telescoping. bioRxiv. 2019;515981.Google Scholar
  26. 26.
    Izquierdo E, Quinkler T, De Renzis S. Guided morphogenesis through optogenetic activation of rho signalling during early Drosophila embryogenesis. Nat Commun. 2018;9:2366.CrossRefGoogle Scholar
  27. 27.
    Krueger D, Tardivo P, Nguyen C, De Renzis S. Downregulation of basal myosin-II is required for cell shape changes and tissue invagination. EMBO J. 2018;37.Google Scholar
  28. 28.
    Wuidart A, Ousset M, Rulands S, Simons BD, Van Keymeulen A, Blanpain C. Quantitative lineage tracing strategies to resolve multipotency in tissue-specific stem cells. Genes Dev. 2016;30:1261–77.CrossRefGoogle Scholar
  29. 29.
    Wuidart A, Sifrim A, Fioramonti M, Matsumura S, Brisebarre A, Brown D, et al. Early lineage segregation of multipotent embryonic mammary gland progenitors. Nat Cell Biol. 2018;20:666–76.CrossRefGoogle Scholar
  30. 30.
    Santoro A, Vlachou T, Carminati M, Pelicci PG, Mapelli M. Molecular mechanisms of asymmetric divisions in mammary stem cells. EMBO Rep. 2016;17:1700–20.CrossRefGoogle Scholar
  31. 31.
    Myllymäki S-M, Mikkola ML. Inductive signals in branching morphogenesis - lessons from mammary and salivary glands. Curr Opin Cell Biol. 2019;61:72–8.CrossRefGoogle Scholar
  32. 32.
    Lloyd-Lewis B, Mourikis P, Fre S. Notch signalling: sensor and instructor of the microenvironment to coordinate cell fate and organ morphogenesis. Curr Opin Cell Biol. 2019;61:16–23.CrossRefGoogle Scholar
  33. 33.
    Koledova Z, Sumbal J. A pleiotropic role for FGF signaling in mammary gland stromal fibroblasts. bioRxiv. 2019;565267.Google Scholar
  34. 34.
    Lerche M, Elosegui-Artola A, Guzmán C, Georgiadou M, Kechagia JZ, Gullberg D, et al. Integrin binding dynamics modulate ligand-specific mechanosensing in mammary gland fibroblasts. bioRxiv. 2019;570721.Google Scholar
  35. 35.
    Marusiak AA, Prelowska MK, Mehlich D, Lazniewski M, Kaminska K, Gorczynski A, et al. Upregulation of MLK4 promotes migratory and invasive potential of breast cancer cells. Oncogene. 2019;38:2860–75.CrossRefGoogle Scholar
  36. 36.
    Koledova Z, Howard BA, Englund J, Bach K, Bentires-Alj M, Gonzalez-Suarez E. European network of breast development and Cancer turned 10 years: a growing family of mammary gland researchers. Breast Cancer Res BCR. 2018;20:102.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of BiomedicineUniversity of BaselBaselSwitzerland
  2. 2.Turku Bioscience CentreUniversity of Turku and Åbo Akademi UniversityTurkuFinland
  3. 3.Cancer Research Laboratory FICAN WestUniversity of Turku and Turku University HospitalTurkuFinland
  4. 4.Developmental Biology Program, Institute of Biotechnology, HiLIFEUniversity of HelsinkiHelsinkiFinland
  5. 5.Department of PharmacologyUniversity of CambridgeCambridgeUK
  6. 6.Department of Biomedicine, Department of SurgeryUniversity Hospital Basel, University of BaselBaselSwitzerland
  7. 7.Department of Histology and Embryology, Faculty of MedicineMasaryk UniversityBrnoCzech Republic

Personalised recommendations