Altered HOX Gene Expression in Human Skin and Breast Cancer Cells

Svingen, Terje; Tonissen, Kathryn Fay

doi:10.4161/cbt.2.5.441

Cited by 50 publications

(36 citation statements)

References 39 publications

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“…In addition, both mRNA levels and protein levels of HOXA1 are significantly correlated with chemotherapy response in human patients. HOXC13 has also been shown to be strongly and progressively expressed in human melanoma and highly expressed in cells of the MCF-7 breast cancer cell line (119,120). Our findings that Hoxa1 and Hoxc13 are direct downstream targets of YAP in the epithelial tissues of developing tooth and the epidermis of skin may provide insights into understanding the molecular mechanisms of YAP in not only organism development but also human disease onset and progression.…”

Section: Discussionmentioning

confidence: 85%

YAP Regulates the Expression of Hoxa1 and Hoxc13 in Mouse and Human Oral and Skin Epithelial Tissues

Liu

Zhao

Lin

et al. 2015

Molecular and Cellular Biology

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c Yes-associated protein (YAP) is a Hippo signaling transcriptional coactivator that plays pivotal roles in stem cell proliferation, organ size control, and tumor development. The downstream targets of YAP have been shown to be highly context dependent. In this study, we used the embryonic mouse tooth germ as a tool to search for the downstream targets of YAP in ectoderm-derived tissues. Yap deficiency in the dental epithelium resulted in a small tooth germ with reduced epithelial cell proliferation. We compared the gene expression profiles of embryonic day 14.5 (E14.5) Yap conditional knockout and YAP transgenic mouse tooth germs using transcriptome sequencing (RNA-Seq) and further confirmed the differentially expressed genes using real-time PCR and in situ hybridization. We found that YAP regulates the expression of Hoxa1 and Hoxc13 in oral and dental epithelial tissues as well as in the epidermis of skin during embryonic and adult stages. Sphere formation assay suggested that Hoxa1 and Hoxc13 are functionally involved in YAP-regulated epithelial progenitor cell proliferation, and chromatin immunoprecipitation (ChIP) assay implies that YAP may regulate Hoxa1 and Hoxc13 expression through TEAD transcription factors. These results provide mechanistic insights into abnormal YAP activities in mice and humans. Y es-associated protein (YAP) is a key transcriptional coactivator of the Hippo signaling pathway that plays pivotal roles in stem/progenitor cell proliferation and organ size control (1-11). YAP has also been shown to be a candidate oncogene in the development and progression of multiple human cancers (12-14). The activity of YAP is negatively regulated by its upstream kinase cascade (MstI/2, Sav1, Lats1/2, and Mob1), which leads to the phosphorylation and subsequent degradation of YAP and its paralog TAZ. Inhibition of Hippo signaling relieves YAP and TAZ, which can then translocate into the nucleus. In the nucleus, YAP or TAZ associates with TEAD or other transcription factors to activate the transcription of its target genes (15-18). Conventional knockout of Yap in mice causes early embryonic lethality due to defects in yolk sac vasculogenesis (19). Overexpression of YAP results in enlarged organ size in Drosophila and in mice with profound cell proliferation and inhibition of apoptosis (1,2,7,11, 20). In addition, YAP also plays a critical role in maintaining mouse embryonic stem cell pluripotency and regulating tissue-specific progenitor cells (21).Although the core components of the Hippo pathway are highly conserved between Drosophila and mammalian systems, the transcriptional outputs differ greatly depending on when and where the pathway is deployed. For example, overexpression of YAP in the mouse small intestine leads to Notch-dependent hyperplasia and loss of terminally differentiated cell types but does not appreciably increase the overall size of the organ (1). In Drosophila, the YAP ortholog Yki induces the expression of cycE, diap1, and bantam microRNA (11, 22). In mammalian cells, YAP induces ...

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Section: Discussionmentioning

confidence: 85%

YAP Regulates the Expression of Hoxa1 and Hoxc13 in Mouse and Human Oral and Skin Epithelial Tissues

Liu

Zhao

Lin

et al. 2015

Molecular and Cellular Biology

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“…A putative role of HOXs in malignant processes has been well documented in leukemia (35)(36)(37). Several HOXs also have been implicated in solid tumors, such as breast, colonic, rectal, gastric, lung, renal, colorectal, cervical and testicular carcinomas (11,(19)(20)(21)(22)(23)(24)(25)(26)(27)(28). It seems that whereas some HOXs have the same expression in normal and malignant tissues, others exhibit altered expression in cancer lesions, suggesting an association with cancer progression.…”

Section: Discussionmentioning

confidence: 99%

“…In humans, 39 HOXs have been identified that are spread in four different clusters located on four separate chromosomes: 7 (HOXA), 17 (HOXB), 12 (HOXC) and 2 (HOXD) (18). Some HOXs, including HOXA10, have been implicated in several solid tumor types (11,(19)(20)(21)(22)(23)(24)(25)(26)(27)(28).…”

Section: Introductionmentioning

confidence: 99%

State of homeobox A10 expression as a putative prognostic marker for oral squamous cell carcinoma

Yamatoji

Kasamatsu²,

Yamano³

et al. 2009

Oncol Rep

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Abstract. Homeobox (HOX) A10, the regulator of embryonic morphogenesis and differentiation, is aberrantly expressed in several cancer types. Our previous study using microarray technology showed that significant up-regulation of HOXA10 occurs in oral squamous cell carcinoma (OSCC)-derived cell lines compared to human normal oral keratinocytes (HNOKs). The aim of the current study was to examine the status of HOXA10 mRNA and protein expression in OSCC-derived cell lines and human primary OSCCs. HOXA10 mRNA was up-regulated in six OSCCderived cell lines compared with HNOKs and in primary OSCCs by using real-time quantitative reverse transcriptasepolymerase chain reaction. Immunohistochemistry data indicated that HOXA10 protein expression levels were consistent with mRNA expression status in OSCC-derived cell lines and primary OSCCs. Furthermore, HOXA10 expression status was correlated with the TNM stage (P<0.05). These results indicate that HOXA10 expression could contribute to cancer progression and prognosis and that HOXA10 may be a potential diagnostic marker and a therapeutic target for OSCCs.

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“…A total of 14/25 genes exhibited differential expression levels in malignant breast tissues compared with non-malignant breast tissues (51). Several studies have demonstrated that various HOX genes are differentially expressed (either up-or downregulated) in patients with breast cancer, indicating the involvement of these genes in carcinogenesis and breast cancer metastasis (43,52,53). In addition, HOXA5 and HOXA9 have been implicated as regulators of p53 and breast cancer 1 (BRCA1), respectively, which are important factors in cancer development (54,55).…”

Section: Hox Genes and Cancermentioning

confidence: 99%

The function of homeobox genes and lncRNAs in cancer

Wang¹,

Dang²,

Liu³

et al. 2016

Oncology Letters

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Abstract. Recently, the homeobox (HOX) gene family has been reported as a factor in tumorigenesis. In the human genome, the HOX gene family contains 4 clusters with 39 genes and multiple transcripts. Mutation or abnormal expression of genes is responsible for developmental disorders. In addition, changes in the levels and activation of certain HOX genes has been associated with the development of cancer. Long non-coding RNAs (lncRNAs) have also been identified to serve critical functions in cancer. Although a limited number of lncRNAs have been previously investigated, the list of functional lncRNA genes has recently grown. Two of the most important and well-studied lncRNAs and HOX transcript genes are HOX transcript antisense RNA (HOTAIR) and HOXA distal transcript antisense RNA (HOTTIP). The present study aimed to review not only the function of the HOTAIR and HOTTIP genes in certain forms of cancer, but also to review other HOX genes and protein functions in cancer, particularly HOX family genes associated with lncRNAs.

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Altered HOX Gene Expression in Human Skin and Breast Cancer Cells

Cited by 50 publications

References 39 publications

YAP Regulates the Expression of Hoxa1 and Hoxc13 in Mouse and Human Oral and Skin Epithelial Tissues

YAP Regulates the Expression of Hoxa1 and Hoxc13 in Mouse and Human Oral and Skin Epithelial Tissues

State of homeobox A10 expression as a putative prognostic marker for oral squamous cell carcinoma

The function of homeobox genes and lncRNAs in cancer

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