Stromal <i>Hoxa5</i> function controls the growth and differentiation of mammary alveolar epithelium

Garin, Élisabeth; Lemieux, Margot; Coulombe, Yan; Robinson, Gertraud W.

doi:10.1002/dvdy.20822

Cited by 38 publications

(15 citation statements)

References 55 publications

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“…PG9 genes, for example, are implicated in mammary gland maturation, expansion and differentiation (Chen and Capecchi, 1999). The control of cell differentiation has also been well documented for Hoxa5 in the mouse, which instructs epithelia from stromal cells in the lungs, gut and mammary gland (Aubin et al, 2002;Boucherat et al, 2012;Garin et al, 2006). In vertebrates, several Hox genes have been shown to either promote or inhibit vascular development or remodelling (Stoll and Kroll, 2012), supporting a general view that Hox proteins directly modulate effector genes involved in the control of cell-cell and cell-extracellular matrix interactions (Kachgal et al, 2012;Winnik et al, 2009).…”

Section: An Overview Of the Hox Gene Familymentioning

confidence: 98%

Cellular and molecular insights into Hox protein action

et al. 2015

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Hox genes encode homeodomain transcription factors that control morphogenesis and have established functions in development and evolution. Hox proteins have remained enigmatic with regard to the molecular mechanisms that endow them with specific and diverse functions, and to the cellular functions that they control. Here, we review recent examples of Hox-controlled cellular functions that highlight their versatile and highly context-dependent activity. This provides the setting to discuss how Hox proteins control morphogenesis and organogenesis. We then summarise the molecular modalities underlying Hox protein function, in particular in light of current models of transcription factor function. Finally, we discuss how functional divergence between Hox proteins might be achieved to give rise to the many facets of their action.

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Section: An Overview Of the Hox Gene Familymentioning

confidence: 98%

Cellular and molecular insights into Hox protein action

et al. 2015

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“…Hoxb5 and Hoxc5 mutant mice are viable and no organ defect has been described (8,43). In contrast, the loss of Hoxa5 function results in a panoply of phenotypes indicative of the broad range of Hoxa5 actions throughout life, including tracheal and lung dysmorphogenesis responsible for the high neonatal mortality rate of Hoxa5 Ϫ/Ϫ pups (1,2,4,17,19,29,36). Surviving Hoxa5 Ϫ/Ϫ mice display an emphysema-like phenotype characterized by air space enlargement and goblet cell metaplasia (33).…”

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confidence: 93%

Partial functional redundancy betweenHoxa5andHoxb5paralog genes during lung morphogenesis

Boucherat

Montaron

Bérubé-Simard

et al. 2013

American Journal of Physiology-Lung Cellular and Molecular Phys

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Hox genes encode transcription factors governing complex developmental processes in several organs. A subset of Hox genes are expressed in the developing lung. Except for Hoxa5, the lack of overt lung phenotype in single mutants suggests that Hox genes may not play a predominant role in lung ontogeny or that functional redundancy may mask anomalies. In the Hox5 paralog group, both Hoxa5 and Hoxb5 genes are expressed in the lung mesenchyme whereas Hoxa5 is also expressed in the tracheal mesenchyme. Herein, we generated Hoxa5;Hoxb5 compound mutant mice to evaluate the relative contribution of each gene to lung development. Hoxa5;Hoxb5 mutants carrying the four mutated alleles displayed an aggravated lung phenotype, resulting in the death of the mutant pups at birth. Characterization of the phenotype highlighted the role of Hoxb5 in lung formation, the latter being involved in branching morphogenesis, goblet cell specification, and postnatal air space structure, revealing partial functional redundancy with Hoxa5. However, the Hoxb5 lung phenotypes were less severe than those seen in Hoxa5 mutants, likely because of Hoxa5 compensation. New specific roles for Hoxa5 were also unveiled, demonstrating the extensive contribution of Hoxa5 to the developing respiratory system. The exclusive expression of Hoxa5 in the trachea and the phrenic motor column likely underlies the Hoxa5-specific trachea and diaphragm phenotypes. Altogether, our observations establish that the Hoxa5 and Hoxb5 paralog genes shared some functions during lung morphogenesis, Hoxa5 playing a predominant role.

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“…In the studies done by Boucherat et al and Garin et al, the immunostaining pattern of HOXA5 was located in the pulmonary epithelium nuclei during the pulmonary development 12,34. However, another study found different expression pattern in the pulmonary malignancy.…”

Section: Discussionmentioning

confidence: 92%

HOXA5 and p53 cooperate to suppress lung cancer cell invasion and serve as good prognostic factors in non-small cell lung cancer

Chang¹,

Chen²,

Hsieh³

et al. 2017

J. Cancer

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Lung cancer is the leading cause of cancer mortality worldwide and tumor metastasis is the major cause of cancer-related death. Our previous study suggested that Homeobox A5 (HOXA5) could inhibit lung cancer cell invasion via regulating cytoskeletal remodeling and involved in tumor metastasis. Recently, consensus HOX binding sites was found in the p53 gene promoter region. However, whether the HOXA5 could cooperate with p53 and contribute the inhibition of lung cancer cell invasion is still unclear. The aim of the current study is to elucidate the correlation of HOXA5 and p53 in tumor invasion and its prognostic influence in lung cancer patient specimens. Totally 71 cases of primary non-small cell lung cancer (NSCLC) were collected. The median follow-up period is 6.8 years. Immunohistochemical stain for p53 and HOXA5 were performed. Kaplan-Meier plot was done for overall survival analysis. In addition, lung cancer cell lines transfected with wild-type or mutated p53 constructs were overexpressed with HOXA5 for invasion assay. In human specimens, HOXA5 expressed mainly in the cytoplasm (54.1%) rather than nuclei (14.6%) of the NSCLC tumor part. The HOXA5 expression is higher in adenocarcinoma than in squamous cell carcinoma (P < 0.001). In addition, poor prognosis is seen in group with both non-immunoreactive for p53 and HOXA5. HOXA5 and p53 could cooperate to inhibit tumor cell invasion significantly partly by decreasing MMP2 activity in a concentration-dependent manner. Our studies provide new insights into how HOXA5 and p53 cooperate to contribute to the suppression of lung cancer cell invasion and play good prognostic roles in NSCLC.

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Stromal Hoxa5 function controls the growth and differentiation of mammary alveolar epithelium

Cited by 38 publications

References 55 publications

Cellular and molecular insights into Hox protein action

Cellular and molecular insights into Hox protein action

Partial functional redundancy betweenHoxa5andHoxb5paralog genes during lung morphogenesis

HOXA5 and p53 cooperate to suppress lung cancer cell invasion and serve as good prognostic factors in non-small cell lung cancer

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