Intratumoral bidirectional transitions between epithelial and mesenchymal cells in triple-negative breast cancer

Dear All,

Cell Signal Unit (Yamamoto Unit) would like to inform you of a seminar by Dr. Jun-ichiro Inoue from The University of Tokyo.

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Date: Wednesday, April 3, 2019

Time: 13:00-14:00

Venue: C016, Level C, Lab 1

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Speaker:

Dr. Jun-ichiro Inoue, The University of Tokyo

Title:
Intratumoral bidirectional transitions between epithelial and mesenchymal cells in triple-negative breast cancer

Abstract:
Epithelial-mesenchymal transition (EMT) and its reverse process, MET, are crucial in several stages of cancer metastasis. EMT allows cancer cells to move to proximal blood vessels for intravasation. However, because EMT and MET processes are dynamic, mesenchymal cancer cells are likely to undergo MET transiently and subsequently re-undergo EMT to restart the metastatic process. Therefore, spatiotemporally-coordinated mutual regulation between EMT and MET could occur during metastasis. To elucidate such regulation, we chose HCC38, a human triple-negative breast cancer cell line, because HCC38 is composed of epithelial and mesenchymal populations at a fixed ratio even though mesenchymal cells proliferate significantly more slowly than epithelial cells. We purified epithelial and mesenchymal cells from Venus-labeled and unlabeled HCC38 and mixed them at various ratios to follow EMT and MET. Using this system, we demonstrate that the efficiency of EMT is about an order of magnitude higher than that of MET and that the two populations significantly enhance the transition of cells from the other population to their own. In addition, knockdown of ZEB1 or SLUG significantly suppressed EMT but promoted partial MET, indicating ZEB1 and SLUG are crucial to EMT and MET. We also demonstrate that primary breast cancer cells underwent EMT that correlated with changes in expression profiles of genes determining EMT status and breast cancer subtype. These changes were very similar to those observed in EMT in HCC38. Consequently, we propose HCC38 as a suitable model to analyze EMT-MET dynamics that could affect development of triple-negative breast cancer.

Host:
Prof. Tadashi Yamamoto

We hope to see many of you at the seminar.

Best regards,

Yuki Nakagawa

Research Unit Administrator

Cell Signal Unit