Evidence map›Paper›PMID 39004623›Full record

ArticleOncogenesis2024

YAP/TAZ interacts with RBM39 to confer resistance against indisulam.

Toshinori Ando, Kento Okamoto, Yume Ueda, Nanako Kataoka, Tomoaki Shintani, Souichi Yanamoto, Mutsumi Miyauchi, Mikihito Kajiya

Abstract read
In one paragraph

Article in Oncogenesis, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed.

  1. Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Toshinori AndoCenter of Oral Clinical Examination, Hiroshima University Hospital, Hiroshima, 734-8551, Japan. toando19@hiroshima-u.ac.jp.ORCID http://orcid.org/0000-0002-3141-8173
Kento OkamotoDepartment of Oral Oncology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, 734-8553, Japan.
Yume UedaDepartment of Oral Oncology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, 734-8553, Japan.
Nanako KataokaCenter of Oral Clinical Examination, Hiroshima University Hospital, Hiroshima, 734-8551, Japan.
Tomoaki ShintaniCenter of Oral Clinical Examination, Hiroshima University Hospital, Hiroshima, 734-8551, Japan.ORCID http://orcid.org/0000-0002-0789-3273
Souichi YanamotoDepartment of Oral Oncology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, 734-8553, Japan.
Mutsumi MiyauchiDepartment of Oral and Maxillofacial Pathobiology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, 734-8553, Japan.
Mikihito KajiyaCenter of Oral Clinical Examination, Hiroshima University Hospital, Hiroshima, 734-8551, Japan.ORCID http://orcid.org/0000-0001-6652-0007

Funding

Japan Society for the Promotion of Science London (JSPS London) JP22H0327500MEXT | Japan Society for the Promotion of Science (JSPS) JP20K18477MEXT | Japan Society for the Promotion of Science (JSPS) JP22H0327500
6 · The paper itself

Abstract

The Hippo pathway and its downstream effectors, Yes-associated protein/transcriptional coactivator with PDZ-binding motif (YAP/TAZ), are essential for cell growth and organ development. Emerging evidence revealed that the Hippo pathway and YAP/TAZ are frequently dysregulated by multiple genetic alterations in solid cancers including head and neck squamous cell carcinoma (HNSCC); however, the YAP/TAZ-nuclear interactome remains unclear. RNA-binding motif protein 39 (RBM39) enhances transcriptional activity of several transcription factors and also regulates mRNA splicing. Indisulam degrading RBM39 induces alternative splicing, leading to cell death. However, clinical trials of indisulam have failed to show effectiveness. Therefore, clarifying the resistance mechanism against splicing inhibitors is urgently required. In this study, we identified RBM39 as a novel YAP/TAZ-interacting molecule by proteome analysis. RBM39 promoted YAP/TAZ transcriptional activity. We further elucidated that indisulam reduces RBM39/YAP/TAZ-mediated integrin or collagen expression, thereby inactivating focal adhesion kinase (FAK) important for cell survival. Moreover, indisulam also induced alternative splicing of cell cycle- or DNA metabolism-related genes. YAP/TAZ hyperactivation delayed indisulam-induced RBM39 degradation, which restored the integrin/collagen expression to activate FAK, and alternative splicing, thereby conferring resistance against indisulam in vitro and in vivo. Our findings may aid to develop a novel cancer therapy focusing on YAP/TAZ/RBM39 interaction.

Identifiers

PMID39004623
PMCPMC11247092

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.