The 14th Workshop of the European Network of Breast Development and Cancer (ENBDC): Methods in Mammary Gland Biology and Breast Cancer Research took place on 27-29 April 2023 in Weggis, Switzerland. Zuzana Sumbalova Koledova, the editor-in-chief of the Journal of Mammary Gland Biology and Neoplasia and a committee member of the ENBDC, attended this meeting. She is honoured to present here two of the three winners of the Best Poster prizes, with a brief overview of these researchers and their research in their own words.
Oliver Benjamin Cottrell
PhD Student, Division of Cancer Sciences, University of Manchester, United Kingdom
Supervised by Nancy Papalopulu and Robert Clarke
Our goal in the Nancy Papalopulu group is to understand the function of oscillatory gene expression in regulating cell state transitions. An oscillation is simply a recurrent, periodic, fluctuation in expression. A growing wealth of transcription factors are understood to be capable of protein-level oscillations. This has important ramifications for gene function. Namely, the same transcription factor can exhibit distinct functional outputs when oscillating compared to ‘sustained’ expression, giving rise to distinct cellular outcomes in each case. Crucially, genes can switch between oscillatory and sustained expression non-genetically. Thus, we propose that non-genetic alteration of expression pattern provides a non-genetic mechanism to vary gene function and cell state.
Until recently, we have primarily investigated this question in neural and developmental systems. Now we are keenly interrogating the role of these oscillations in phenotypic plasticity of tumours, such as that seen in re-emergence from dormancy. This is typified by ER+ breast cancer cells which stochastically re-awaken from long-term dormant micrometastases. We believe this transition must be a non-genetic event, as non-proliferative cells cannot acquire a mutational burden. But how do cells achieve this? We hypothesise that changing between oscillatory and sustained expression may underpin the non-genetic cell state transition seen in stochastic emergence from dormancy.
Using a range of cutting edge molecular-biology and time-lapse live-imaging techniques, we have shown a key transcription factor, HES1, oscillates over the course of the cell cycle in proliferative MCF7 cells. We suggest the function of this oscillation is to control cell cycle progression by regulating p21 dynamics. Moreover, this oscillation is lost in arrested cells and returns following re-emergence. Together, we propose oscillatory HES1 is critical for cell cycle progression and thus manipulating its expression pattern represents a therapeutic opportunity to control transitions between quiescence and proliferation.
Postdoc, Laboratory for Intravital Imaging and Dynamics of Tumor Progression, VIB Center for Cancer Biology, KU Leuven, Leuven, Belgium
Supervised by Colinda L.G.J. Scheele
Our lab, led by Prof. Colinda Scheele focuses on morphogenesis, homeostasis, and tumorigenesis of epithelial organs. Our research spans from cellular-level studies to the scale of entire organs. The overarching goal of our lab is to understand how healthy tissue architecture and environment prevent or promote the different steps of tumorigenesis. For my project, I am exploring how natural changes in the human breast throughout a woman’s life can influence susceptibility to breast cancer. It's well established that breast tissue continually remodels itself during key hormonal events such as puberty, pregnancy, lactation, and recurrent menstrual cycles, all these to accommodate specific functional requirements based on a woman's physiological state. Now, I hypothesize that each developmental stage might differently influence tumour initiation and progression. However, due to the lack of dynamic models that mimic the distinct breast developmental stages, the cellular mechanisms driving this susceptibility remain unclear. To bridge this knowledge gap, I am working on developing 3D in vitro breast organoid models derived from human primary tissue that mimic the stages of the female reproductive life cycle. Another key milestone necessary to better explore healthy breast biology is the generation of novel healthy breast cell lines. In collaboration with ENBDC members, we have been working to engineer a panel of fluorescently labelled breast cell lines from our collected tissues. We are hopeful that our immortalized breast cancer panel will help to alleviate the chronic shortage of breast tissue samples within the scientific community.