Abstract
Homeobox (HOX) transcription factors, encoded by a subset of homeodomain superfamily genes, play pivotal roles in many aspects of cellular physiology, embryonic development, and tissue homeostasis. Findings over the past decade have revealed that mutations in HOX genes can lead to increased cancer predisposition, and HOX genes might mediate the effect of many other cancer susceptibility factors by recognizing or executing altered genetic information. Remarkably, several lines of evidence highlight the interplays between HOX transcription factors and cancer risk loci discovered by genome-wide association studies, thereby gaining molecular and biological insight into cancer etiology. In addition, deregulated HOX gene expression impacts various aspects of cancer progression, including tumor angiogenesis, cell autophagy, proliferation, apoptosis, tumor cell migration, and metabolism. In this review, we will discuss the fundamental roles of HOX genes in cancer susceptibility and progression, highlighting multiple molecular mechanisms of HOX involved gene misregulation, as well as their potential implications in clinical practice.
Highlights
The homeobox genes encode a highly conserved family of transcription factors that play essential roles in embryonic development and tissue homeostasis
This study demonstrated that HOXA13 is a target gene transforming the roles of risk regulatory single nucleotide polymorphism (SNP) at the 7p15.2 locus that influences prostate cancer susceptibility
Current evidence emerging from functional elucidation of regulatory risk SNPs show that transcription factors are usually involved in the recognition and execution of genetic information implicated in cancer risk-associated genetic variations, thereby leading to altered gene expression and increased cancer susceptibility [46,48]
Summary
The homeobox genes encode a highly conserved family of transcription factors that play essential roles in embryonic development and tissue homeostasis. Accumulating evidence shows that functional abnormalities of HOX transcription factors play critical roles in the development and progression of many types of cancers [1,2]. Both mutation and aberrant expression can alter the function of the HOX transcription factor by gene regulation, and subsequently affect downstream events of cancer development. Aberrant expression of HOXA9 was proven to play critical roles in the development of acute leukemia through reprogramming the epigenome or synergizing with other transcription factors and signaling pathways, thereby considered as one of the driving forces in leukemogenesis [5,6]. We briefly discuss clinical implications of HOX proteins as cancer therapeutic targets
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