The Role of the CREB Signaling Pathway in Tumor Development and Therapeutic Potential

Abstract

Review The Role of the CREB Signaling Pathway in Tumor Development and Therapeutic Potential Qunlong Jin 1,2,†, Youheng Jiang 1,2,†, Zhiheng Zhang 1,3,†, Yanming Yang 1, Zhang Fu 1, Yunfeng Gao 1,4, Ningning Li 1,5, Yulong He 2,*, and Changxue Li 1,2,* 1 Tomas Lindahl Nobel Laureate Laboratory, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, 518107, China 2 Digestive Diseases Center, Guangdong Provincial Key Laboratory of Digestive Cancer Research, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, 518107, China 3 The Affiliated High School of Shenzhen University, Shenzhen, 518066, China 4 Department of Otolaryngology, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, 518107, China 5 China-UK Institute for Frontier Science, Shenzhen, 518107, China † These authors contributed equally to this work. * Correspondence: heyulong@mail.sysu.edu.cn (Y.L.H.); lichx59@mail2.sysu.edu.cn (C.X.L.) Received: 2 May 2024; Revised: 19 May 2024; Accepted: 20 May 2024; Published: 11 June 2024 Abstract: The cAMP response element-binding protein (CREB) is a multifunctional transcription factor belonging to the basic leucine zipper (bZIP) family of proteins. It regulates the expression of target genes by binding to the cAMP response element (CRE) on DNA. The activation of CREB in cells typically depends on its phosphorylation, mediated by kinases activated by various signaling pathways, such as the cAMP-dependent protein kinase A (PKA) pathway and the PI3K-AKT pathway. CREB regulates genes involved in various cellular functions, including cell growth, differentiation, survival, as well as the development and plasticity of the nervous system. Therefore, CREB plays a key role in the development of neurological diseases, oncology, and other diseases. This review aims to systematically elucidate the structure and regulatory mechanisms of CREB, its biological function in tumors, and the potential of targeting the CREB signaling pathway in anti-tumor therapy, with the hope of providing new strategies and targets for cancer treatment.