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±Û¾´ÀÌ °ü¸®ÀÚ ÀÛ¼ºÀÏ 2019-05-13 12:46:24
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kuho@kumc.or.kr
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2019-05-13 12:46:24

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* ÁÖÁ¦ :  Hippo signaling in organ size control, homeostasis, and cancer

Seminar Abstract
Precise organ size control is required in both embryonic development and adult tissue
regeneration and is ensured by tight regulation of duration and progression of cell division, disruption
of which leads to devastating diseases including tumor formation. The recently discovered Hippo
signaling pathway has gained interest as being critical regulators of cancer progression, besides its
fundamental functions in tissue growth/organ size control and regeneration. In this seminar, I will
present two interesting stories about 1) novel regulatory mechanism of Hippo pathway 2) signaling
network of interacting pathways and tumor microenvironment caused by Hippo pathway during liver
tumorigenesis.


1) Abnormal regulation of Hippo signaling is linked to a variety of human diseases, including cancer.
Owing to the importance of Hippo signaling in a wide range of biological fields, a better understanding
of its precise mechanisms could provide fundamental insights for therapeutic applications. Although
many studies have extensively investigated the regulation of Hippo signaling, our knowledge remains
insufficient due to the complexity and diversity of Hippo pathway. It is generally accepted that the
identification of novel regulators and their functions is a prerequisite to fully elucidating the regulation
of Hippo pathway. Recently, we reported several novel modulators of Hippo pathway in controlling
organ size and tumor development. In this seminar, I would like to discuss the mechanistic regulation
of Hippo pathway by focusing on the roles of these novel regulators.


2) We found that the Hippo, Wnt/¥â-catenin and Notch pathways form an interacting network in
maintaining liver size and suppressing hepatocellular carcinoma (HCC). Ablation of Hippo kinase
Mst1 and Mst2 in liver leads to rapid HCC formation and activates Yap, Wnt/¥â-catenin and Notch
signaling, each one of these downstream events can lead to HCC. Rigorous genetic experiments
revealed that in the Hippo deficient liver, Notch signaling forms a positive feedback loop with Hippo
signaling effector Yap, which promotes severe hepatomegaly and rapid HCC initiation and
progression. Surprisingly, Wnt/¥â-catenin signaling activation suppresses HCC formation by inhibiting
the positive feedback loop between Yap and Notch signaling. In addition, we observed that Hippo
pathway suppresses protumoral immune responses by inhibiting expression of chemokine Ccl2.
Furthermore, we have observed strong correlation between Ccl2 expression and Yap transcription
signature in HCC patients









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