A Case of Identity: HOX Genes in Normal and Cancer Stem Cells

Abstract

Stem cells are undifferentiated cells that have the unique ability to self-renew and differentiate into many different cell types. Their function is controlled by core gene networks whose misregulation can result in aberrant stem cell function and defects of regeneration or neoplasia. HOX genes are master regulators of cell identity and cell fate during embryonic development. They play a crucial role in embryonic stem cell differentiation into specific lineages and their expression is maintained in adult stem cells along differentiation hierarchies. Aberrant HOX gene expression is found in several cancers where they can function as either oncogenes by sustaining cell proliferation or tumor-suppressor genes by controlling cell differentiation. Emerging evidence shows that abnormal expression of HOX genes is involved in the transformation of adult stem cells into cancer stem cells. Cancer stem cells have been identified in most malignancies and proved to be responsible for cancer initiation, recurrence, and metastasis. In this review, we consider the role of HOX genes in normal and cancer stem cells and discuss how the modulation of HOX gene function could lead to the development of novel therapeutic strategies that target cancer stem cells to halt tumor initiation, progression, and resistance to treatment.

The vascular nature of lung-resident mesenchymal stem cells

“…[43][44][45] The characteristic embryonic HOX gene expression profiles, the so-called "HOX code," is sustained in adults, where HOX genes regulate cell specification and tissue differentiation according to the body region. 46 Accordingly, the topographical specificity of HOX genes is maintained in tissue-typical MSCs and further on after differentiation, which indicates that HOX genes are decisive for the specification of MSC identity. As HOX gene expression profiles mirrors that of the developmental origin of MSCs, HOX gene expression can be used to distinguish different stem cell populations and in particular MSCs of functionally distinct tissues.…”

Some Questions and Answers About the Role of Hox Temporal Collinearity in Vertebrate Axial Patterning

“…The study by Faiella et al (1994) also first demonstrated the PI Hox-Hox interaction. Recent pubications (Seifert et al, 2015; Smith et al, 2019) have emphasized that Hox genes are important in regulating ES stem cell directionality. The cells involved in the embryo clearly include pluripotent stem cells too.…”

Quantitative Analysis of Differential Expression of HOX Genes in Multiple Cancers

“…Multiple reports have demonstrated that mis-regulation of HOX genes expression plays key roles in the development of cancers. Only in the last five years have more than 50 reviews related to this subject been published; see, for example, References [4,[8][9][10][11]. However, such studies were typically based on different technologies used in different labs and analyzed by different computational tools.…”