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Involvement of COUP-TFs in Cancer Progression.

Boudot A, Le Dily F, Pakdel F - Cancers (Basel) (2011)

Bottom Line: Although COUP-TFs are expressed in a wide range of tissues in adults, little is known about their functions at later stages of development or in organism homeostasis.COUP-TFs are expressed in cancer cell lines of various origins and increasing studies suggest they play roles in cell fate determination and, potentially, in cancer progression.Nevertheless, the exact roles of COUP-TFs in these processes remain unclear and even controversial.

View Article: PubMed Central - PubMed

Affiliation: Molecular and Cellular Interactions, UMR CNRS 6026, IFR 140 GFSA, University of Rennes 1, Rennes, France. farzad.pakdel@univ-rennes1.fr.

ABSTRACT
The orphan receptors COUP-TFI and COUP-TFII are members of the nuclear receptor superfamily that play distinct and critical roles in vertebrate organogenesis, as demonstrated by loss-of-function COUP-TFI and/or COUP-TFII mutant mice. Although COUP-TFs are expressed in a wide range of tissues in adults, little is known about their functions at later stages of development or in organism homeostasis. COUP-TFs are expressed in cancer cell lines of various origins and increasing studies suggest they play roles in cell fate determination and, potentially, in cancer progression. Nevertheless, the exact roles of COUP-TFs in these processes remain unclear and even controversial. In this review, we report both in vitro and in vivo data describing known and suspected actions of COUP-TFs that suggest that these factors are involved in modification of the phenotype of cancer cells, notably of epithelial origin.

No MeSH data available.


Related in: MedlinePlus

Principal biological processes controlled by COUP-TFs during embryogenesis that suggest a role of these factors during cancer progression. Biological processes that could promote cancer progression are linked by red arrows, while those that could promote regression of cancer are connected by green arrows. During embryonic development, COUP-TFs are key regulators of various processes that are also linked to cancer progression. Several downstream targets of these factors are connected to angiogenesis, cell growth or mobility which could be linked to cancer cell growth and metastatic potential. Moreover, both COUP-TFs are able to interfere with nuclear receptor signaling which are known to play critical roles during hormone-dependent cancers development. On the other hand, depending on the circumstance, COUP-TFs also control some biological aspects that could be associated with cancer regression. These orphan NRs were reported to control cell cycle arrest to support neuronal differentiation, or to contribute to RA dependent differentiation. NRs, nuclear receptors; RA, retinoic acid.
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f2-cancers-03-00700: Principal biological processes controlled by COUP-TFs during embryogenesis that suggest a role of these factors during cancer progression. Biological processes that could promote cancer progression are linked by red arrows, while those that could promote regression of cancer are connected by green arrows. During embryonic development, COUP-TFs are key regulators of various processes that are also linked to cancer progression. Several downstream targets of these factors are connected to angiogenesis, cell growth or mobility which could be linked to cancer cell growth and metastatic potential. Moreover, both COUP-TFs are able to interfere with nuclear receptor signaling which are known to play critical roles during hormone-dependent cancers development. On the other hand, depending on the circumstance, COUP-TFs also control some biological aspects that could be associated with cancer regression. These orphan NRs were reported to control cell cycle arrest to support neuronal differentiation, or to contribute to RA dependent differentiation. NRs, nuclear receptors; RA, retinoic acid.

Mentions: Most of the reported actions of COUP-TFs occur during embryonic development during which COUP-TFI and COUP-TFII have been shown to exert specific and redundant activities. Levels of expression of both COUP-TFs decrease after organogenesis but these receptors remains ubiquitously expressed in adults, suggesting that they still have a role at later stages of development in normal and potentially pathological biological processes. Indeed, re-activation of the embryonic network is often observed during cancer development, as illustrated by epithelial-mesenchymal-transition (EMT). The process of EMT, which consists of the loss of cell-cell contacts and polarized-epithelial characteristics for the acquisition of a fibroblastic and dedifferentiated-mesenchymal phenotype, is an essential step for carcinoma cells to metastasize [39,40]. The variety of COUP-TFs effects that we have described above suggest that these NRs could be involved in these events. For instance, COUP-TF's impacts on cell fate determination strongly suggest that these NRs may play a role in cancer progression by influencing the differentiation of cancer cells or by determining their proliferative behavior. COUP-TFs are proposed to control many biological functions involved in cell migration such as cell-cell contacts and adhesion as well as synthesis of the extracellular matrix (ECM) components. These processes are highly related to cancer progression, through modulation of metastatic potential of cancer cells. In addition, since angiogenesis is one of the fundamental steps of cancers progression, a direct connection between COUP-TFs and this biological process is in line with a contribution of these NRs in disease progression (Figure 2).


Involvement of COUP-TFs in Cancer Progression.

Boudot A, Le Dily F, Pakdel F - Cancers (Basel) (2011)

Principal biological processes controlled by COUP-TFs during embryogenesis that suggest a role of these factors during cancer progression. Biological processes that could promote cancer progression are linked by red arrows, while those that could promote regression of cancer are connected by green arrows. During embryonic development, COUP-TFs are key regulators of various processes that are also linked to cancer progression. Several downstream targets of these factors are connected to angiogenesis, cell growth or mobility which could be linked to cancer cell growth and metastatic potential. Moreover, both COUP-TFs are able to interfere with nuclear receptor signaling which are known to play critical roles during hormone-dependent cancers development. On the other hand, depending on the circumstance, COUP-TFs also control some biological aspects that could be associated with cancer regression. These orphan NRs were reported to control cell cycle arrest to support neuronal differentiation, or to contribute to RA dependent differentiation. NRs, nuclear receptors; RA, retinoic acid.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3756385&req=5

f2-cancers-03-00700: Principal biological processes controlled by COUP-TFs during embryogenesis that suggest a role of these factors during cancer progression. Biological processes that could promote cancer progression are linked by red arrows, while those that could promote regression of cancer are connected by green arrows. During embryonic development, COUP-TFs are key regulators of various processes that are also linked to cancer progression. Several downstream targets of these factors are connected to angiogenesis, cell growth or mobility which could be linked to cancer cell growth and metastatic potential. Moreover, both COUP-TFs are able to interfere with nuclear receptor signaling which are known to play critical roles during hormone-dependent cancers development. On the other hand, depending on the circumstance, COUP-TFs also control some biological aspects that could be associated with cancer regression. These orphan NRs were reported to control cell cycle arrest to support neuronal differentiation, or to contribute to RA dependent differentiation. NRs, nuclear receptors; RA, retinoic acid.
Mentions: Most of the reported actions of COUP-TFs occur during embryonic development during which COUP-TFI and COUP-TFII have been shown to exert specific and redundant activities. Levels of expression of both COUP-TFs decrease after organogenesis but these receptors remains ubiquitously expressed in adults, suggesting that they still have a role at later stages of development in normal and potentially pathological biological processes. Indeed, re-activation of the embryonic network is often observed during cancer development, as illustrated by epithelial-mesenchymal-transition (EMT). The process of EMT, which consists of the loss of cell-cell contacts and polarized-epithelial characteristics for the acquisition of a fibroblastic and dedifferentiated-mesenchymal phenotype, is an essential step for carcinoma cells to metastasize [39,40]. The variety of COUP-TFs effects that we have described above suggest that these NRs could be involved in these events. For instance, COUP-TF's impacts on cell fate determination strongly suggest that these NRs may play a role in cancer progression by influencing the differentiation of cancer cells or by determining their proliferative behavior. COUP-TFs are proposed to control many biological functions involved in cell migration such as cell-cell contacts and adhesion as well as synthesis of the extracellular matrix (ECM) components. These processes are highly related to cancer progression, through modulation of metastatic potential of cancer cells. In addition, since angiogenesis is one of the fundamental steps of cancers progression, a direct connection between COUP-TFs and this biological process is in line with a contribution of these NRs in disease progression (Figure 2).

Bottom Line: Although COUP-TFs are expressed in a wide range of tissues in adults, little is known about their functions at later stages of development or in organism homeostasis.COUP-TFs are expressed in cancer cell lines of various origins and increasing studies suggest they play roles in cell fate determination and, potentially, in cancer progression.Nevertheless, the exact roles of COUP-TFs in these processes remain unclear and even controversial.

View Article: PubMed Central - PubMed

Affiliation: Molecular and Cellular Interactions, UMR CNRS 6026, IFR 140 GFSA, University of Rennes 1, Rennes, France. farzad.pakdel@univ-rennes1.fr.

ABSTRACT
The orphan receptors COUP-TFI and COUP-TFII are members of the nuclear receptor superfamily that play distinct and critical roles in vertebrate organogenesis, as demonstrated by loss-of-function COUP-TFI and/or COUP-TFII mutant mice. Although COUP-TFs are expressed in a wide range of tissues in adults, little is known about their functions at later stages of development or in organism homeostasis. COUP-TFs are expressed in cancer cell lines of various origins and increasing studies suggest they play roles in cell fate determination and, potentially, in cancer progression. Nevertheless, the exact roles of COUP-TFs in these processes remain unclear and even controversial. In this review, we report both in vitro and in vivo data describing known and suspected actions of COUP-TFs that suggest that these factors are involved in modification of the phenotype of cancer cells, notably of epithelial origin.

No MeSH data available.


Related in: MedlinePlus