YES1 Is a Targetable Oncogene in Cancers Harboring YES1 Gene Amplification

Cancer Research
Natsuki HamanakaToshiyuki Mio

Abstract

Targeting genetic alterations of oncogenes by molecular-targeted agents (MTA) is an effective approach for treating cancer. However, there are still no clinical MTA options for many cancers, including esophageal cancer. We used a short hairpin RNA library to screen for a new oncogene in the esophageal cancer cell line KYSE70 and identified YES proto-oncogene 1 (YES1) as having a significant impact on tumor growth. An analysis of clinical samples showed that YES1 gene amplification existed not only in esophageal cancer but also in lung, head and neck, bladder, and other cancers, indicating that YES1 would be an attractive target for a cancer drug. Because there is no effective YES1 inhibitor so far, we generated a YES1 kinase inhibitor, CH6953755. YES1 kinase inhibition by CH6953755 led to antitumor activity against YES1-amplified cancers in vitro and in vivo. Yes-associated protein 1 (YAP1) played a role downstream of YES1 and contributed to the growth of YES1-amplified cancers. YES1 regulated YAP1 transcription activity by controlling its nuclear translocation and serine phosphorylation. These findings indicate that the regulation of YAP1 by YES1 plays an important role in YES1-amplified cancers and that CH6953755 has therapeu...Continue Reading

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Citations

May 29, 2020·Technology in Cancer Research & Treatment·Guochen ZhangXiangdong Bai
Jan 28, 2021·Molecular Systems Biology·Aurelien DugourdJulio Saez-Rodriguez
Apr 27, 2021·Frontiers in Psychiatry·Kaitlin E BountressAnanda B Amstadter
Jun 9, 2021·British Journal of Cancer·Margot De MarcoLiberato Marzullo
Sep 28, 2021·Molecular Systems Biology·Hasmik KeshishianSteven A Carr

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