YAP as a New Oncogene and a Mechanoresponder

Dear All,

Cell Signal Unit (Yamamoto Unit) would like to inform you of a seminar by Dr. Marius Sudol, Icahn School of Medicine at Mount Sinai (USA).

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Date: Wednesday, January 27, 2021

Time: 10:00-11:00

Venue: C700, Level C, Lab 3

             ZOOM: https://oist.zoom.us/j/97352393640?pwd=TkRBeW1qMU1SQUpZbk80OUVGYTh6Zz09

             Meeting ID: 973 5239 3640

             *If you need the passcode, please send e-mail to yuki.nakagawa[at]oist.jp.

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Speaker:

Dr. Marius Sudol, Icahn School of Medicine at Mount Sinai (USA)

Title:
YAP as a New Oncogene and a Mechanoresponder

Abstract:

YAP (Yes kinase-associated protein) is a WW domain-containing protein that acts as a potent oncogene and stemness factor.  It is one of the two main effectors of the Hippo tumor suppressor pathway. YAP is a transforming gene of the chromosome 11q22 amplicon, and its expression is elevated at high frequency in human cancers, including liver, breast, ovary, and stomach cancer. When the YAP gene is fused to a transcription factor gene known as TFE3, it causes a soft tissue sarcoma that is classified as epithelioid hemangioendothelioma that targets primarily the liver and lungs.

YAP regulates the actomyosin network by suppressing Rho-GTPase via Rho-GTPase activating protein 29 (ARHGAP29) that is a direct transcriptional target of YAP in human gastric cancer. YAP directly promotes the expression of ARHGAP29 to suppress the RhoA-LIMK-cofilin pathway, thereby destabilizing F-actin. The overexpression of YAP causes cytoskeletal rearrangement by altering the dynamics of F-actin/G-actin turnover, thus promoting cell migration. In a mouse model, circulating tumor cells (CTCs) exhibit an increase in ARHGAP29 RNA level compared with the cells at primary tumor sites. Moreover, increased ARHGAP29 expression correlates with shortened survival of human gastric cancer patients. Importantly, ARHGAP29 is critical in regulating cancer metastasis, as shown in a mouse model of liver cancer metastasizing to lungs.

Cancer cells are generally softer than normal cells. By increasing the rigidity of cancer cells to the level of normal cells via novel therapeutic interventions, we could provide a rather unorthodox modality to treat cancer in unison with other standard therapies.

Host:
Prof. Tadashi Yamamoto

We hope to see many of you at the seminar.

Best regards,

Yuki Nakagawa

Research Unit Administrator

Cell Signal Unit