2. Academic Validation
  3. Tolfenamic acid negatively regulates YAP and TAZ expression in human cancer cells

Tolfenamic acid negatively regulates YAP and TAZ expression in human cancer cells

  • Biochim Biophys Acta Mol Cell Res. 2023 Aug 4;119556. doi: 10.1016/j.bbamcr.2023.119556.
Ilju Kim 1,  Pattawika Lertpatipanpong 1,  Yongdae Yoon 1,  Jaehak Lee 1,  Yukyung Hong 1,  Kanokkan Boonruang 1,  Junsun Ryu 2,  Seung Joon Baek 3
Affiliations

Affiliations

  • 1 College of Veterinary Medicine and Research Institute for Veterinary Science, Seoul National University, Seoul, Republic of Korea.
  • 2 Department of Otolaryngology-Head and Neck Surgery, Center for Thyroid Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Republic of Korea.
  • 3 College of Veterinary Medicine and Research Institute for Veterinary Science, Seoul National University, Seoul, Republic of Korea. Electronic address: [email protected].
PMID: 37544381 DOI: 10.1016/j.bbamcr.2023.119556
Abstract

Several diseases are associated with improper regulation of the Hippo pathway, which plays an important role in cell proliferation and Cancer metastasis. Overactivation of the YAP and TAZ proteins accelerates cell proliferation, invasion, and migration during tumorigenesis. Tolfenamic acid (TA) is a non-steroidal anti-inflammatory drug (NSAID) that exhibits activity against various types of Cancer. In this study, we observed that TA decreased YAP and TAZ protein levels in Cancer cells. TA increased the phosphorylation of YAP and TAZ, leading to the degradation of YAP and TAZ in the cytoplasm and nucleus. TA predominantly affected multiple phosphodegron sites in the YAP and TAZ and lowered 14-3-3β protein expression, causing YAP and TAZ to enter the ubiquitination pathway. Proteins that affect YAP and TAZ regulation, such as NAG-1 and several YAP/TAZ E3 Ligases, were not involved in TA-mediated YAP/TAZ degradation. In summary, our results indicate that TA affects phosphodegron sites on YAP/TAZ, demonstrating a novel effect of TA in tumorigenesis.

Keywords

14-3-3; Anti-cancer; Hippo pathway; NAG-1; TAZ; YAP.

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