The AP-2 Family of Transcription Factors—Still Undervalued Regulators in Gastroenterological Disorders

Yu, Yi-Jin; Kołat, Damian; Kałuzińska-Kołat, Żaneta; Liang, Zhu; Peng, Bo-Qiang; Zhu, Yun-Feng; Liu, Kai; Mei, Jia-Xin; Yu, Gang; Zhang, Wei-Han; Chen, Xiao-Long; Yang, Kun; Hu, Jian-Kun; Zhao, Lin-Yong

doi:10.3390/ijms25179138

Open AccessReview

The AP-2 Family of Transcription Factors—Still Undervalued Regulators in Gastroenterological Disorders

by

Yi-Jin Yu

^1,2

,

Damian Kołat

^3,4

,

Żaneta Kałuzińska-Kołat

^3,4

,

Zhu Liang

^5,6,

Bo-Qiang Peng

^1,2,

Yun-Feng Zhu

^1,2,

Kai Liu

^1,2,

Jia-Xin Mei

^1,2,

Gang Yu

^1,2,

Wei-Han Zhang

^1,2,

Xiao-Long Chen

^1,2,

Kun Yang

^1,2,

Jian-Kun Hu

^1,2 and

Lin-Yong Zhao

^1,2,*

¹

Department of General Surgery & Laboratory of Gastric Cancer, State Key Laboratory of Biotherapy–Collaborative Innovation Center of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, China

²

Gastric Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, China

³

Department of Functional Genomics, Medical University of Lodz, 90-752 Lodz, Lodzkie, Poland

⁴

Department of Biomedicine and Experimental Surgery, Medical University of Lodz, 90-136 Lodz, Lodzkie, Poland

⁵

Nuffield Department of Medicine, Target Discovery Institute, University of Oxford, Center for Medicines Discovery, Oxford OX1 2JD, UK

⁶

Nuffield Department of Medicine, Chinese Academy of Medical Sciences (CAMS), CAMS Oxford Institute (COI), University of Oxford, Oxford OX1 2JD, UK

^*

Author to whom correspondence should be addressed.

Int. J. Mol. Sci. 2024, 25(17), 9138; https://doi.org/10.3390/ijms25179138

Submission received: 23 June 2024 / Revised: 27 July 2024 / Accepted: 14 August 2024 / Published: 23 August 2024

(This article belongs to the Special Issue Molecular Research of Gastrointestinal Disease 2.0)

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Abstract

Activating enhancer-binding protein 2 (AP-2) is a family of transcription factors (TFs) that play crucial roles in regulating embryonic and oncogenic development. In addition to splice isoforms, five major family members encoded by the TFAP2A/B/C/D/E genes have been identified in humans, i.e., AP-2α/β/γ/δ/ε. In general, the first three TFs have been studied more thoroughly than AP-2δ or AP-2ε. Currently, there is a relatively limited body of literature focusing on the AP-2 family in the context of gastroenterological research, and a comprehensive overview of the existing knowledge and recommendations for further research directions is lacking. Herein, we have collected available gastroenterological data on AP-2 TFs, discussed the latest medical applications of each family member, and proposed potential future directions. Research on AP-2 in gastrointestinal tumors has predominantly been focused on the two best-described family members, AP-2α and AP-2γ. Surprisingly, research in the past decade has highlighted the importance of AP-2ε in the drug resistance of gastric cancer (GC) and colorectal cancer (CRC). While numerous questions about gastroenterological disorders await elucidation, the available data undoubtedly open avenues for anti-cancer targeted therapy and overcoming chemotherapy resistance. In addition to gastrointestinal cancers, AP-2 family members (primarily AP-2β and marginally AP-2γ) have been associated with other health issues such as obesity, type 2 diabetes, liver dysfunction, and pseudo-obstruction. On the other hand, AP-2δ has been poorly investigated in gastroenterological disorders, necessitating further research to delineate its role. In conclusion, despite the limited attention given to AP-2 in gastroenterology research, pivotal functions of these transcription factors have started to emerge and warrant further exploration in the future.

Keywords: AP-2; TFAP2; transcription factors; gastroenterological disorders; gastric cancer; colorectal cancer

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MDPI and ACS Style

Yu, Y.-J.; Kołat, D.; Kałuzińska-Kołat, Ż.; Liang, Z.; Peng, B.-Q.; Zhu, Y.-F.; Liu, K.; Mei, J.-X.; Yu, G.; Zhang, W.-H.; et al. The AP-2 Family of Transcription Factors—Still Undervalued Regulators in Gastroenterological Disorders. Int. J. Mol. Sci. 2024, 25, 9138. https://doi.org/10.3390/ijms25179138

AMA Style

Yu Y-J, Kołat D, Kałuzińska-Kołat Ż, Liang Z, Peng B-Q, Zhu Y-F, Liu K, Mei J-X, Yu G, Zhang W-H, et al. The AP-2 Family of Transcription Factors—Still Undervalued Regulators in Gastroenterological Disorders. International Journal of Molecular Sciences. 2024; 25(17):9138. https://doi.org/10.3390/ijms25179138

Chicago/Turabian Style

Yu, Yi-Jin, Damian Kołat, Żaneta Kałuzińska-Kołat, Zhu Liang, Bo-Qiang Peng, Yun-Feng Zhu, Kai Liu, Jia-Xin Mei, Gang Yu, Wei-Han Zhang, and et al. 2024. "The AP-2 Family of Transcription Factors—Still Undervalued Regulators in Gastroenterological Disorders" International Journal of Molecular Sciences 25, no. 17: 9138. https://doi.org/10.3390/ijms25179138

APA Style

Yu, Y.-J., Kołat, D., Kałuzińska-Kołat, Ż., Liang, Z., Peng, B.-Q., Zhu, Y.-F., Liu, K., Mei, J.-X., Yu, G., Zhang, W.-H., Chen, X.-L., Yang, K., Hu, J.-K., & Zhao, L.-Y. (2024). The AP-2 Family of Transcription Factors—Still Undervalued Regulators in Gastroenterological Disorders. International Journal of Molecular Sciences, 25(17), 9138. https://doi.org/10.3390/ijms25179138

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The AP-2 Family of Transcription Factors—Still Undervalued Regulators in Gastroenterological Disorders

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