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Sox4 links tumor suppression to accelerated aging in mice [Hair regeneration]

ABSTRACT: Sox4 is a transcription factor expressed during embryonic development and some adult tissues such as lymphoid organs, pancreas, intestine and skin. During embryogenesis, Sox4 regulates the survival of mesenchymal and neural progenitors, lymphocyte and myeloid differentiation, and pancreatic, bone and cardiac development. Aberrantly increased Sox4 expression is linked to malignant transformation and metastasis in several types of human cancer. To study the role of Sox4 in the adult organism, we first generated mice with reduced whole-body Sox4 expression. These mice display a plethora of age-related degenerative disorders and reduced spontaneous cancer incidence, indicating a role for this protein in maintaining adult tissue homeostasis and in tumor growth. To specifically address a role for Sox4 in adult stem cells, we conditionally deleted Sox4 (Sox4cKO) in stratified epithelia. Sox4cKO mice show increased skin stem cell quiescence and DNA damage accumulation, accompanied by resistance to chemical carcinogenesis. These phenotypes correlate with downregulation of cell cycle, DNA repair and skin stem cell genes in the absence of Sox4. Altogether, these findings highlight the importance of Sox4 in adult tissue homeostasis and cancer.

ORGANISM(S): Mus musculus

PROVIDER: GSE58153 | GEO | 2015/05/20

SECONDARY ACCESSION(S): PRJNA251399

REPOSITORIES: GEO

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Sox4 links tumor suppression to accelerated aging in mice [Telogen]

Project description:Sox4 is a transcription factor expressed during embryonic development and some adult tissues such as lymphoid organs, pancreas, intestine and skin. During embryogenesis, Sox4 regulates the survival of mesenchymal and neural progenitors, lymphocyte and myeloid differentiation, and pancreatic, bone and cardiac development. Aberrantly increased Sox4 expression is linked to malignant transformation and metastasis in several types of human cancer. To study the role of Sox4 in the adult organism, we first generated mice with reduced whole-body Sox4 expression. These mice display a plethora of age-related degenerative disorders and reduced spontaneous cancer incidence, indicating a role for this protein in maintaining adult tissue homeostasis and in tumor growth. To specifically address a role for Sox4 in adult stem cells, we conditionally deleted Sox4 (Sox4cKO) in stratified epithelia. Sox4cKO mice show increased skin stem cell quiescence and DNA damage accumulation, accompanied by resistance to chemical carcinogenesis. These phenotypes correlate with downregulation of cell cycle, DNA repair and skin stem cell genes in the absence of Sox4. Altogether, these findings highlight the importance of Sox4 in adult tissue homeostasis and cancer. Sox4 WT and cKO (conditional KO in skin) skin was collected for microarray hybridization, to study the contribution of Sox4 to skin homeostasis in basal conditions (Telogen)

2015-05-20 | E-GEOD-58154 | biostudies-arrayexpress

Sox4 links tumor suppression to accelerated aging in mice [Hair regeneration]

Project description:Sox4 is a transcription factor expressed during embryonic development and some adult tissues such as lymphoid organs, pancreas, intestine and skin. During embryogenesis, Sox4 regulates the survival of mesenchymal and neural progenitors, lymphocyte and myeloid differentiation, and pancreatic, bone and cardiac development. Aberrantly increased Sox4 expression is linked to malignant transformation and metastasis in several types of human cancer. To study the role of Sox4 in the adult organism, we first generated mice with reduced whole-body Sox4 expression. These mice display a plethora of age-related degenerative disorders and reduced spontaneous cancer incidence, indicating a role for this protein in maintaining adult tissue homeostasis and in tumor growth. To specifically address a role for Sox4 in adult stem cells, we conditionally deleted Sox4 (Sox4cKO) in stratified epithelia. Sox4cKO mice show increased skin stem cell quiescence and DNA damage accumulation, accompanied by resistance to chemical carcinogenesis. These phenotypes correlate with downregulation of cell cycle, DNA repair and skin stem cell genes in the absence of Sox4. Altogether, these findings highlight the importance of Sox4 in adult tissue homeostasis and cancer. Sox4 WT and cKO (conditional KO in skin) were plucked and skin was collected for microarray hibridization, to study the contribution of Sox4 to hair regeneration and hair follicle stem cell activation

2015-05-20 | E-GEOD-58153 | biostudies-arrayexpress

Sox4 links tumor suppression to accelerated aging in mice [Telogen]

2015-05-20 | GSE58154 | GEO

Transcriptomic analysis of intestinal epithelial Sox4 knockout

Project description:Sox4 is expressed in intestinal stem cells (ISCs) and early intestinal progenitors. The regulatory role for Sox4 in intestinal homeostasis is currently unknown. Here, we used RNA-seq to determine the role of Sox4 in the intestinal epithelium using a conditional knockout model.

2018-11-22 | GSE90795 | GEO

SOX4 supports cancer stemness by enhancing HDAC1 transcription revealed by comparative proteomics

Project description:We have investigated the proteome changes induced by SOX4 overexpression in HCT-116 cells using iTRAQ-based quantitative proteomics. Bioinformatics analysis revealed that HDAC1 could be one of the important regulators in cancer stem cells (CSCs) maintenance. We found that SOX4 transcriptionally regulates HDAC1 to support the stemness of cancer stem cells (CSCs). This work revealed a novel underlying mechanism, SOX4-HDAC1 axis, for stemness maintenance of human cancer.

2021-09-09 | PXD019694 | Pride

siRNA profiling of human LNCaP cells transfected with SOX4 cDNA, SOX4 siRNA or GFP cDNA

Project description:SOX4 is a critical developmental transcription factor in vertebrates and is required for precise differentiation and proliferation in multiple tissues. In addition, SOX4 is overexpressed in many human malignancies, but the precise role of SOX4 in cancer progression is not well understood. Here we have either eliminated SOX4 using siRNA or overexpressed a SOX4 cDNA and compared the gene expression patterns against control GFP transfections to identify SOX4 target genes. Data described in manuscript P. Liu et al., Cancer Res 46, 4011 (April 15, 2006) Experiment Overall Design: LNCaP prostate cancer cells were transfected with either a SOX4 cDNA, a pool of SOX4 siRNAs or a control GFP expression vector. Each transfection was performed in duplicate on two separate days. Total RNA was harvested 24 hours post-transfection

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Expression data for T24 bladder cancer cell line - scrambled, SOX4-KD and SOX4 overexpression

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Sox4 in adult hepatocytes

Project description:Sox4 in adult hepatocytes

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Expression data from LNCaP cells transfected with SOX4 cDNA, SOX4 siRNA or GFP cDNA

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Identification of SOX4 novel transcriptional targets.

Project description:The SOX4 gene belongs to a family of transcription factors and we previously unveiled SOX4 gene amplification and over-expression in a subset of lung cancers, indicating it may constitute a driver oncogene. Here, we searched for SOX4 transcriptional targets and investigate their involvement in lung development and carcinogenesis. We abrogated SOX4 expression in the NIH-H522 lung cancer cell line, carrying SOX4 amplification and over-expression, using an inducible short-hairpin system. Global analysis of gene expression identified about 90 genes down-regulated after SOX4 abrogation many of them related to neural development. We also demonstrated recruitment of SOX4 to many of these promoters, evidencing their nature as direct transcriptional targets of SOX4. Most of these transcripts were significantly increased in lung cancer cells with ectopic SOX4 over-expression and in lung tumors with high levels of SOX4. Conversely, many of them exhibited significant low expression levels in embryonic fibroblasts from Sox4-/- mice.

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