Targeting sine oculis homeoprotein 1 (SIX1): A review of oncogenic roles and potential natural product therapeutics
Zhiwei Bian,
Menny M. Benjamin,
Lucas Bialousow,
Yintai Tian,
G. Aaron Hobbs,
Dev Karan,
Yeun-Mun Choo,
Mark T. Hamann,
Xiaojuan Wang
Affiliations
Zhiwei Bian
School of Pharmacy, Lanzhou University, Lanzhou, 730000, Gansu, China
Menny M. Benjamin
Drug Discovery and Biomedical Sciences, Medical University of South Carolina, Charleston, SC, USA
Lucas Bialousow
Drug Discovery and Biomedical Sciences, Medical University of South Carolina, Charleston, SC, USA
Yintai Tian
School of Pharmacy, Lanzhou University, Lanzhou, 730000, Gansu, China
G. Aaron Hobbs
School of Pharmacy, Lanzhou University, Lanzhou, 730000, Gansu, China; Drug Discovery and Biomedical Sciences, Medical University of South Carolina, Charleston, SC, USA; Department of Pathology, Medical College of Wisconsin, Milwaukee, WI, USA; Hollings Cancer Center, Medical University of South Carolina, Charleston, SC, USA; Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, Charleston, SC, USA; Chemistry Department, Faculty of Science, University of Malaya, 50603, Kuala Lumpur, Malaysia
Dev Karan
Department of Pathology, Medical College of Wisconsin, Milwaukee, WI, USA
Yeun-Mun Choo
Chemistry Department, Faculty of Science, University of Malaya, 50603, Kuala Lumpur, Malaysia; Corresponding author.
Mark T. Hamann
Drug Discovery and Biomedical Sciences, Medical University of South Carolina, Charleston, SC, USA; Corresponding author.
Xiaojuan Wang
School of Pharmacy, Lanzhou University, Lanzhou, 730000, Gansu, China; Corresponding author.
Sine oculis homeoprotein 1 (SIX1), a prominent representative of the homeodomain transcription factors within the SIX family, has attracted significant interest owing to its role in tumorigenesis, cancer progression, and prognostic assessments. Initially recognized for its pivotal role in embryonic development, SIX1 has emerged as a resurgent factor across a diverse set of mammalian cancers. Over the past two decades, numerous investigations have emphasized SIX1's dual significance as a developmental regulator and central player in oncogenic processes. A mounting body of evidence links SIX1 to the initiation of diverse cancers, encompassing enhanced cellular metabolism and advancement. This review provides an overview of the multifaceted roles of SIX1 in both normal development and oncogenic processes, emphasizing its importance as a possible therapeutic target and prognostic marker. Additionally, this review discusses the natural product agents that inhibit various pro-oncogenic mechanisms associated with SIX1.
