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Hox transcription factors: modulators of cell-cell and cell-extracellular matrix adhesion.

Taniguchi Y - Biomed Res Int (2014)

Bottom Line: Hox genes encode homeodomain-containing transcription factors that determine cell and tissue identities in the embryo during development.Hox genes are also expressed in various adult tissues and cancer cells.In this review, the potential roles Hox proteins play in cell adhesion and migration during vertebrate body patterning are discussed.

View Article: PubMed Central - PubMed

Affiliation: Division of Basic Molecular Science and Molecular Medicine, School of Medicine, Tokai University, Isehara, Kanagawa 259-1193, Japan.

ABSTRACT
Hox genes encode homeodomain-containing transcription factors that determine cell and tissue identities in the embryo during development. Hox genes are also expressed in various adult tissues and cancer cells. In Drosophila, expression of cell adhesion molecules, cadherins and integrins, is regulated by Hox proteins operating in hierarchical molecular pathways and plays a crucial role in segment-specific organogenesis. A number of studies using mammalian cultured cells have revealed that cell adhesion molecules responsible for cell-cell and cell-extracellular matrix interactions are downstream targets of Hox proteins. However, whether Hox transcription factors regulate expression of cell adhesion molecules during vertebrate development is still not fully understood. In this review, the potential roles Hox proteins play in cell adhesion and migration during vertebrate body patterning are discussed.

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Related in: MedlinePlus

Transition from epithelial to mesenchymal morphology caused by HOXD3 expression in lung cancer A549 cells. A549 cells stably transfected with empty vector (A549-vec) or HOXD3 expression vector (A549-HOXD3) [33] were fixed and stained for nuclei and F-actin by using DAPI and phalloidin-rhodamine, respectively. A549-vec cells have epithelial morphology (a, b), while A549-HOXD3 cells have spindle-shape mesenchymal morphology (c, d). A reduction in E-cadherin expression and an increase in α3 and β3 integrin expression were observed in A549-HOXD3 cells, as compared to A549-vec cells [33].
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fig2: Transition from epithelial to mesenchymal morphology caused by HOXD3 expression in lung cancer A549 cells. A549 cells stably transfected with empty vector (A549-vec) or HOXD3 expression vector (A549-HOXD3) [33] were fixed and stained for nuclei and F-actin by using DAPI and phalloidin-rhodamine, respectively. A549-vec cells have epithelial morphology (a, b), while A549-HOXD3 cells have spindle-shape mesenchymal morphology (c, d). A reduction in E-cadherin expression and an increase in α3 and β3 integrin expression were observed in A549-HOXD3 cells, as compared to A549-vec cells [33].

Mentions: In contrast, HOXD3 overexpression in lung cancer A549 cells transforms them from epithelial to mesenchymal morphology (Figure 2) and causes a simultaneous reduction in E-cadherin expression levels and increase in α3 and β3 expression [33]. This was the first study reporting that HOX gene expression enhances the invasive and metastatic properties of human cancer cells. Primary breast carcinomas and distant metastases of various organs exhibit significantly higher HOXB7 expression levels than normal mammary epithelial cells [51]. Overexpression of HOXB7 in MCF10A cells, an immortalized cell line derived from normal human mammary epithelial cells, induces their transformation from cobblestone-like epithelial morphology to spindle-shape mesenchymal morphology, which brings about a dramatic reduction in expression of E-cadherin and tight junction proteins, claudin 1, claudin 4, and claudin 7, as well as an elevation in α-smooth muscle actin expression [51]. Similarly, HOXB9 overexpression in MCF10A cells transforms them from an epithelial phenotype into a mesenchymal phenotype by reducing E-cadherin expression levels and increasing vimentin expression [52]. These findings suggest that HOXD3, HOXB7, and HOXB9 transcription factors serve as EMT inducers in immortalized cells and cancer cells.


Hox transcription factors: modulators of cell-cell and cell-extracellular matrix adhesion.

Taniguchi Y - Biomed Res Int (2014)

Transition from epithelial to mesenchymal morphology caused by HOXD3 expression in lung cancer A549 cells. A549 cells stably transfected with empty vector (A549-vec) or HOXD3 expression vector (A549-HOXD3) [33] were fixed and stained for nuclei and F-actin by using DAPI and phalloidin-rhodamine, respectively. A549-vec cells have epithelial morphology (a, b), while A549-HOXD3 cells have spindle-shape mesenchymal morphology (c, d). A reduction in E-cadherin expression and an increase in α3 and β3 integrin expression were observed in A549-HOXD3 cells, as compared to A549-vec cells [33].
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4127299&req=5

fig2: Transition from epithelial to mesenchymal morphology caused by HOXD3 expression in lung cancer A549 cells. A549 cells stably transfected with empty vector (A549-vec) or HOXD3 expression vector (A549-HOXD3) [33] were fixed and stained for nuclei and F-actin by using DAPI and phalloidin-rhodamine, respectively. A549-vec cells have epithelial morphology (a, b), while A549-HOXD3 cells have spindle-shape mesenchymal morphology (c, d). A reduction in E-cadherin expression and an increase in α3 and β3 integrin expression were observed in A549-HOXD3 cells, as compared to A549-vec cells [33].
Mentions: In contrast, HOXD3 overexpression in lung cancer A549 cells transforms them from epithelial to mesenchymal morphology (Figure 2) and causes a simultaneous reduction in E-cadherin expression levels and increase in α3 and β3 expression [33]. This was the first study reporting that HOX gene expression enhances the invasive and metastatic properties of human cancer cells. Primary breast carcinomas and distant metastases of various organs exhibit significantly higher HOXB7 expression levels than normal mammary epithelial cells [51]. Overexpression of HOXB7 in MCF10A cells, an immortalized cell line derived from normal human mammary epithelial cells, induces their transformation from cobblestone-like epithelial morphology to spindle-shape mesenchymal morphology, which brings about a dramatic reduction in expression of E-cadherin and tight junction proteins, claudin 1, claudin 4, and claudin 7, as well as an elevation in α-smooth muscle actin expression [51]. Similarly, HOXB9 overexpression in MCF10A cells transforms them from an epithelial phenotype into a mesenchymal phenotype by reducing E-cadherin expression levels and increasing vimentin expression [52]. These findings suggest that HOXD3, HOXB7, and HOXB9 transcription factors serve as EMT inducers in immortalized cells and cancer cells.

Bottom Line: Hox genes encode homeodomain-containing transcription factors that determine cell and tissue identities in the embryo during development.Hox genes are also expressed in various adult tissues and cancer cells.In this review, the potential roles Hox proteins play in cell adhesion and migration during vertebrate body patterning are discussed.

View Article: PubMed Central - PubMed

Affiliation: Division of Basic Molecular Science and Molecular Medicine, School of Medicine, Tokai University, Isehara, Kanagawa 259-1193, Japan.

ABSTRACT
Hox genes encode homeodomain-containing transcription factors that determine cell and tissue identities in the embryo during development. Hox genes are also expressed in various adult tissues and cancer cells. In Drosophila, expression of cell adhesion molecules, cadherins and integrins, is regulated by Hox proteins operating in hierarchical molecular pathways and plays a crucial role in segment-specific organogenesis. A number of studies using mammalian cultured cells have revealed that cell adhesion molecules responsible for cell-cell and cell-extracellular matrix interactions are downstream targets of Hox proteins. However, whether Hox transcription factors regulate expression of cell adhesion molecules during vertebrate development is still not fully understood. In this review, the potential roles Hox proteins play in cell adhesion and migration during vertebrate body patterning are discussed.

Show MeSH
Related in: MedlinePlus