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Signaling Networks Involved in the Malignant Transformation of Breast Cancer

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Methods of Mathematical Oncology (MMDS 2020)

Part of the book series: Springer Proceedings in Mathematics & Statistics ((PROMS,volume 370))

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Abstract

Breast cancer stem cells (CSCs) are involved the malignant transformation of breast cancer, including metastasis, because they are more stress-resistant and have higher tumorigenicity than the surrounding breast cancer cells (non-CSCs). We aimed to elucidate the various signaling networks involved in the transformation of mammary epithelial cells into tumor cells based on literature review. We found that constitutive activation of the NF-\({\upkappa}{\text{B}}\) pathway maintains CSCs in basal-like breast cancer, a subtype of triple-negative breast cancer, where NF-\({\upkappa}{\text{B}}\)-mediated induction of JAG1 in non-CSCs results in the stimulation of Notch signaling in CSCs. On the other hand, epithelial-mesenchymal transition (EMT) and its reverse reaction, mesenchymal-epithelial transition (MET), are thought to be involved in breast cancer cell metastasis, which makes elucidating their regulatory mechanisms essential. We identified HCC38, a basal-like breast cancer cell line, as a suitable model to investigate such mechanisms, because EMT and MET are in intratumoral equilibrium with each other in HCC38. In the HCC38 study, we found that multiple signaling pathways between epithelial and mesenchymal cells are involved in the regulation of the dynamic equilibrium between EMT and MET. Mathematical simulation of these intracellular and intercellular signaling networks involved in the malignant transformation of breast cancer could lead to the elucidation of the mechanisms of tumor malignant transformation and the development of therapeutic targets.

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Acknowledgments

We thank Kinuyo Miyazaki, and Yoko Hirayama for their secretarial and research assistance. This work was supported in part by grants-in-aid from the Ministry of Education, Culture, Sports, Science, and Technology Japan (16H06575 to JI), from the Japan Society for the Promotion of Science (18K15235 and 20K07610 to MY; 20H03441 to TA).

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Authors and Affiliations

  1. Research Center for Asian Infectious Diseases, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan

    Mizuki Yamamoto

  2. The University of Tokyo, Tokyo, Japan

    Jun-ichiro Inoue

Authors
  1. Mizuki Yamamoto
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  2. Jun-ichiro Inoue
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Corresponding author

Correspondence to Mizuki Yamamoto .

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Editors and Affiliations

  1. Centre for Mathematical Modeling and Data Science, Osaka University, Toyonaka, Japan

    Takashi Suzuki

  2. Research Team MONC, Institut de Mathématiques de Bordeaux (CNRS UMR 5251), Talence, France

    Clair Poignard

  3. School of Mathematics and Statistics, MI, University of St Andrews, St Andrews, UK

    Mark Chaplain

  4. Quantitative Systems Biology Center, Vanderbilt University School of Medicine, Nashville, TN, USA

    Vito Quaranta

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Yamamoto, M., Inoue, Ji. (2021). Signaling Networks Involved in the Malignant Transformation of Breast Cancer. In: Suzuki, T., Poignard, C., Chaplain, M., Quaranta, V. (eds) Methods of Mathematical Oncology. MMDS 2020. Springer Proceedings in Mathematics & Statistics, vol 370. Springer, Singapore. https://doi.org/10.1007/978-981-16-4866-3_17

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