Potential of targeting signal-transducing adaptor protein-2 in cancer therapeutic applications - Open Access Mini Review

Sep 21, 2026

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Adaptor proteins regulate multiple intracellular signaling pathways, and signal-transducing adaptor protein-2 (STAP-2) contains PH and SH2 domains plus a C-terminal YXXQ motif that binds STAT3. STAP-2/BRK expression is dysregulated in breast cancer, enhancing STAT3-dependent proliferation. In prostate cancer cells, STAP-2 stabilizes EGFR by interacting with BRK/EGFR after stimulation, promoting EGFR signaling that drives growth and progression. Blocking STAP-2 interactions via inhibitory peptides suppresses STAP-2/EGFR binding, EGFR stabilization, and cancer-cell growth, including reduced tumor formation in xenograft models for prostate and lung cancers.

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Exploration of Targeted Anti-tumor Therapy Open Access Mini Review Potential of targeting signal-transducing adaptor protein-2 in cancer therapeutic applications Taiga Maemoto1, Yuto Sasaki1 , Fumiya Okuyama1, Yuichi Kitai1, Kenji Oritani2 , Tadashi Matsuda1* 1Department of Immunology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan 2Departmrnt of Hematology, International University of Health and Welfare, Narita 286-8686, Japan *Correspondence: Tadashi Matsuda, Department of Immunology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita-Ku Kita 12 Nishi 6, Sapporo 060-0812, [Japan.](Japan. tmatsuda@pharm.hokudai.ac.jp)[ tmatsuda@pharm.hokudai.ac.jp](Japan. tmatsuda@pharm.hokudai.ac.jp)[ ](Japan. tmatsuda@pharm.hokudai.ac.jp)[Academic Editor:](Academic Editor: Nicola Normanno)[ Nicola Normanno](Academic Editor: Nicola Normanno), [Istituto Nazionale Tumori-IRCCS-Fondazione G. Pascale](Istituto Nazionale Tumori-IRCCS-Fondazione G. Pascale), [Italy](Italy)[ ](Italy)[Received:](Received: November 1)[ November 1](Received: November 1), 2023 Accepted: January 15, 2024 Published: March 7, 2024 Cite this article: Maemoto T, Sasaki Y, Okuyama F, Kitai Y, Oritani K, Matsuda T. Potential of targeting signal-transducing adaptor protein-2 in cancer therapeutic applications. Explor Target Antitumor Ther. 2024;5:251–9. [https://doi.org/10](https://doi.org/10) . 37349/etat.2024.00216 Abstract Adaptor proteins play essential roles in various intracellular signaling pathways. Signal-transducing adaptor protein-2 (STAP-2) is an adaptor protein that possesses pleckstrin homology (PH) and Srchomology 2 (SH2) domains, as well as a YXXQ signal transducer and activator of transcription 3 (STAT3) -binding motif in its C-terminal region. STAP-2 is also a substrate of breast tumor kinase (BRK) . STAP-2/BRK expression is deregulated in breast cancers and enhances STAT3-dependent cell proliferation. In prostate cancer cells, STAP-2 interacts with and stabilizes epidermal growth factor receptor (EGFR) after stimulation, resulting in the upregulation of EGFR signaling, which contributes to cancer-cell proliferation and tumor progression. Therefore, inhibition of the interaction between STAP-2 and BRK/EGFR may be a possible therapeutic strategy for these cancers. For this purpose, peptides that interfere with STAP- 2/BRK/EGFR binding may have great potential. Indeed, the identified peptide inhibitor successfully suppressed the STAP-2/EGFR protein interaction, EGFR stabilization, and cancer-cell growth. Furthermore, the peptide inhibitor suppressed tumor formation in human prostate-and lung-cancer cell lines in a murine xenograft model. This review focuses on the inhibitory peptide as a promising candidate for the treatment of prostate and lung cancers. Keywords Signal-transducing adaptor protein, signal transduction, epidermal growth factor receptor, prostate cancer, lung cancer, peptides Introduction Most prostate cancer cases are responsive to androgen deprivation or anti-androgen therapy because tumor growth is highly dependent on androgens [1] . However, cancer-cell proliferation becomes resistant to androgen deprivation in some cases after long-term use of androgen-targeted drugs. This results in © The Author(s) 2024. This is an Open Access article licensed under a Creative Commons Attribution 4.0 International License ([https://creativecommons.org/licenses/by/4.0/](https://creativecommons.org/licenses/by/4.0/)), which permits unrestricted use, sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. Explor Target Antitumor Ther. 2024;5:251–9 | [https://doi.org/10.37349/etat.2024.00216](https://doi.org/10.37349/etat.2024.00216) Page 251 androgen-ind

FAQs

What roles do adaptor proteins and STAP-2 play in intracellular signaling?

Adaptor proteins control diverse intracellular signaling pathways. STAP-2 is an adaptor with PH and SH2 domains and a C-terminal STAT3-binding motif, linking it to signaling regulation.

How does STAP-2 contribute to cancer progression through BRK/EGFR?

In prostate cancer cells, STAP-2 interacts with and stabilizes EGFR after stimulation, which upregulates EGFR signaling and supports tumor cell proliferation and progression.

Why are inhibitory peptides proposed as a therapeutic strategy?

Peptides that interfere with STAP-2/BRK/EGFR binding suppress STAP-2/EGFR interaction, reduce EGFR stabilization, inhibit cancer-cell growth, and can reduce tumor formation in xenograft models.

Sep 21, 2026

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