Homeobox Genes in Cancers: From Carcinogenesis to Recent Therapeutic Intervention

Feng, Yangyang; Zhang, Tongyue; Wang, Yijun; Xie, Meng; Ji, Xiaoyu; Luo, Xun-Jiang; Huang, Wenjie; Xia, Limin

doi:10.3389/fonc.2021.770428

Cited by 50 publications

(32 citation statements)

References 169 publications

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“…Within these scenarios, data sharing through the so-called blockchain technology is becoming increasingly necessary, which would improve not only the insights of researchers and clinicians; it could also serve as a suitable basis for an efficient and effective evidence-based decision-making process in therapeutic approaches, as reasoned from other diseases ( Dubovitskaya et al, 2020 ; Fusco et al, 2020 ). For the current state of knowledge on the roles of HOX genes in human cancer the following review articles were recommended ( Bhatlekar et al, 2018 ; Smith et al, 2019 ; Paco et al, 2020 ; Feng et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

HOX genes in stem cells: Maintaining cellular identity and regulation of differentiation

Steens

Klein

2022

Front. Cell Dev. Biol.

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Stem cells display a unique cell type within the body that has the capacity to self-renew and differentiate into specialized cell types. Compared to pluripotent stem cells, adult stem cells (ASC) such as mesenchymal stem cells (MSCs) and hematopoietic stem cells (HSCs) exhibit restricted differentiation capabilities that are limited to cell types typically found in the tissue of origin, which implicates that there must be a certain code or priming determined by the tissue of origin. HOX genes, a subset of homeobox genes encoding transcription factors that are generally repressed in undifferentiated pluripotent stem cells, emerged here as master regulators of cell identity and cell fate during embryogenesis, and in maintaining this positional identity throughout life as well as specifying various regional properties of respective tissues. Concurrently, intricate molecular circuits regulated by diverse stem cell-typical signaling pathways, balance stem cell maintenance, proliferation and differentiation. However, it still needs to be unraveled how stem cell-related signaling pathways establish and regulate ASC-specific HOX expression pattern with different temporal-spatial topography, known as the HOX code. This comprehensive review therefore summarizes the current knowledge of specific ASC-related HOX expression patterns and how these were integrated into stem cell-related signaling pathways. Understanding the mechanism of HOX gene regulation in stem cells may provide new ways to manipulate stem cell fate and function leading to improved and new approaches in the field of regenerative medicine.

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Section: Introductionmentioning

confidence: 99%

HOX genes in stem cells: Maintaining cellular identity and regulation of differentiation

Steens

Klein

2022

Front. Cell Dev. Biol.

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“…Homeobox (HOX) genes are responsible for embryogenesis, morphogenesis, tumorigenesis and cell differentiation [ 41 , 42 ]. Hitherto, four chromosomal clusters of the HOX family, HOXA, HOXB, HOXC, and HOXD, were reported.…”

Section: Discussionmentioning

confidence: 99%

HTRA1 Regulates Subclinical Inflammation and Activates Proangiogenic Response in the Retina and Choroid

Ahamed

Pan

et al. 2022

IJMS

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High-temperature requirement A1 (HtrA1) has been identified as a disease-susceptibility gene for age-related macular degeneration (AMD) including polypoidal choroidal neovasculopathy (PCV). We characterized the underlying phenotypic changes of transgenic (Tg) mice expressing ubiquitous CAG promoter (CAG-HtrA1 Tg). In vivo imaging modalities and histopathology were performed to investigate the possible neovascularization, drusen formation, and infiltration of macrophages. Subretinal white material deposition and scattered white-yellowish retinal foci were detected on CFP [(Tg—33% (20/60) and wild-type (WT)—7% (1/15), p < 0.05]. In 40% (4/10) of the CAG-HtrA1 Tg retina, ICGA showed punctate hyperfluorescent spots. There was no leakage on FFA and OCTA failed to confirm vascular flow signals from the subretinal materials. Increased macrophages and RPE cell migrations were noted from histopathological sections. Monocyte subpopulations were increased in peripheral blood in the CAG-HtrA1 Tg mice (p < 0.05). Laser induced CNV in the CAG-HtrA1 Tg mice and showed increased leakage from CNV compared to WT mice (p < 0.05). Finally, choroidal explants of the old CAG-HtrA1 Tg mice demonstrated an increased area of sprouting (p < 0.05). Signs of subclinical inflammation was observed in CAG-HtrA1 Tg mice. Such subclinical inflammation may have resulted in increased RPE cell activation and angiogenic potential.

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“…HXR9 causes apoptosis in multiple breast cancer cell lines ( Morgan et al, 2012 ). Overcoming the functional redundancies among the different HOX family members is one of the main challenges for HOX-based therapeutic strategies ( Feng et al, 2021 ).…”

Section: Signaling Pathways In Embryonic Mammary Gland Development An...mentioning

confidence: 99%

Embryonic Programs in Cancer and Metastasis—Insights From the Mammary Gland

Lee

2022

Front. Cell Dev. Biol.

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Cancer is characterized as a reversion of a differentiated cell to a primitive cell state that recapitulates, in many aspects, features of embryonic cells. This review explores the current knowledge of developmental mechanisms that are essential for embryonic mouse mammary gland development, with a particular focus on genes and signaling pathway components that are essential for the induction, morphogenesis, and lineage specification of the mammary gland. The roles of these same genes and signaling pathways in mammary gland or breast tumorigenesis and metastasis are then summarized. Strikingly, key embryonic developmental pathways are often reactivated or dysregulated during tumorigenesis and metastasis in processes such as aberrant proliferation, epithelial-to-mesenchymal transition (EMT), and stem cell potency which affects cellular lineage hierarchy. These observations are in line with findings from recent studies using lineage tracing as well as bulk- and single-cell transcriptomics that have uncovered features of embryonic cells in cancer and metastasis through the identification of cell types, cell states and characterisation of their dynamic changes. Given the many overlapping features and similarities of the molecular signatures of normal development and cancer, embryonic molecular signatures could be useful prognostic markers for cancer. In this way, the study of embryonic development will continue to complement the understanding of the mechanisms of cancer and aid in the discovery of novel therapeutic targets and strategies.

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Homeobox Genes in Cancers: From Carcinogenesis to Recent Therapeutic Intervention

Cited by 50 publications

References 169 publications

HOX genes in stem cells: Maintaining cellular identity and regulation of differentiation

HOX genes in stem cells: Maintaining cellular identity and regulation of differentiation

HTRA1 Regulates Subclinical Inflammation and Activates Proangiogenic Response in the Retina and Choroid

Embryonic Programs in Cancer and Metastasis—Insights From the Mammary Gland

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