The versatile functions of Sox9 in development, stem cells, and human diseases

Jo, Alice; Denduluri, Sahitya K.; Zhang, Bosi; Wang, Zhongliang; Liang, Yin; Zhang, Yan; Kang, Richard W.; Shi, Lewis L.; Mok, Ji Oh; Lee, Michael J.; Haydon, Rex C.

doi:10.1016/j.gendis.2014.09.004

Cited by 277 publications

(208 citation statements)

References 142 publications

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“…Dysregulation of SOX9 contributes to the development of different malignant cancers and causes developmental disorders (31,(34)(35)(36). For example, haploinsufficiency for Sox9 causes campomelic dysplasia (CMD) (31, 37-39), a rare neonatal chondrodysplasia characterized by bowing and angulation of long bones and many other skeletal and extraskeletal features (31). The few CMD survivors have disproportionate short stature, progressive kyphoscoliosis, and hip dislocation, among other findings (39), thus sharing phenotypic overlap with Shohat-type SEMD patients.…”

Section: Discussionmentioning

confidence: 99%

Loss of DDRGK1 modulates SOX9 ubiquitination in spondyloepimetaphyseal dysplasia

Egunsola¹,

Bae²,

Jiang³

et al. 2017

Journal of Clinical Investigation

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Section: Discussionmentioning

confidence: 99%

Loss of DDRGK1 modulates SOX9 ubiquitination in spondyloepimetaphyseal dysplasia

Egunsola¹,

Bae²,

Jiang³

et al. 2017

Journal of Clinical Investigation

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“…Of note, several factors, such as POU2F1, DLX4, BCL11A, KLF5, GATA3, AIRE and FLH2 are involved in governing stem cell functions (self-renewal, cell fate specification, cell survival under stress). [57][58][59][60][61][62][63] Only a few miRNAs were found to be putative upstream regulators of proteins present in MSC and Muse cell secretomes (Table 3). In detail, mir-122 and mir-133 appear related to functions ascribed to secretomes of MSCs and Muse cells, such as remodeling of extracellular matrix, metabolic processes and stemness control.…”

Section: Muse Cells Secrete Factors That May Play a Role In Stem Cellmentioning

confidence: 99%

The secretome of MUSE cells contains factors that may play a role in regulation of stemness, apoptosis and immunomodulation

et al. 2016

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Mesenchymal stromal cells (MSCs) are a heterogeneous population, which contain several cell phenotypes: mesenchymal stem cells, progenitor cells, fibroblasts and other type of cells. Previously, we identified unique stem cells that we named multilineage-differentiating stress enduring (Muse) cells as one to several percent of MSCs of the bone marrow, adipose tissue and dermis. Among different cell populations in MSCs, Muse cells, positive for pluripotent surface marker SSEA-3, may represent cells responsible for pluripotent-like property of MSCs, since they express pluripotency genes, able to differentiated into triploblastic cells from a single cells and are self-renewable.MSCs release biologically active factors that have profound effects on local cellular dynamics. A thorough examination of MSC secretome seems essential for understanding the physiological functions exerted by these cells in our organism and also for rational cellular therapy design. In this setting, studies on secretome of Muse cells may shed light on pathways that are associated with their specific features.Our findings evidenced that secretomes of MSCs and Muse cells contain factors that regulate extracellular matrix remodeling, ox-redox activities and immune system. Muse cells appear to secrete factors that may preserve their stem cell features, allow survival under stress conditions and may contribute to their immunomodulation capacity.In detail, the proteins belonging to protein kinase A signaling, FXR/RXR activation and LXR/RXR activation pathways may play a role in regulation of Muse stem cell features. These last 2 pathways together with proteins associated with antigen presentation pathway and coagulation system may play a role in immunomodulation.

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“…SOX9, plays vital roles in embryonic development (19). The importance of SOX9 in tumorigenesis has been identified, and the dysregulation of SOX9 has been implicated in several cancers, including prostate cancer, lung adenocarcinoma and gastric carcinoma (20)(21)(22).…”

Section: Discussionmentioning

confidence: 99%

Inï¿½vitro study on the role of SOX9 in trastuzumab resistance of adenocarcinoma of the esophagogastric junction

et al. 2018

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Abstract. Trastuzumab is recommended for the treatment of human epidermal growth factor receptor 2-positive adenocarcinoma of the esophagogastric junction (AEG) in combination with chemotherapy; however, drug resistance has severely affected its clinical application. The present study aimed to investigate the effect of sex determining region Y-box 9 (SOX9), a prognostic marker in adjuvant oncological settings, on AEG cell proliferation and apoptosis in the presence or absence of trastuzumab. Furthermore, the molecular mechanism underlying the role of SOX9 in trastuzumab resistance was explored. ESO26 cells were treated with various concentrations of trastuzumab, and trastuzumab induced SOX9 expression in a concentration-dependent manner, as determined by reverse transcription-quantitative polymerase chain reaction and western blotting analyses. Transfection of ESO26 cells with SOX9 small interfering RNA was conducted to knock down SOX9 expression, and the results of MTT and flow cytome try assays demonstrated that SOX9 knockdown sensitized ESO26 cells to trastuzumab by inhibiting cell proliferation and enhancing cell apoptosis. In addition, it was observed that the trastuzumab-induced phosphorylation of AKT was suppressed by SOX9 knockdown. In conclusion, the present study demonstrated that SOX9 participated in trastuzumab resistance by affecting cell proliferation and apoptosis, and indicated that SOX9 may exert its effect on trastuzumab resistance via activation of the phosphatidylinositol-3-kinase/AKT signaling pathway. This study identified a novel mechanism underlying trastuzumab resistance in vitro and may be useful in improving the efficacy of trastuzumab treatment. IntroductionAdenocarcinoma of the esophagogastric junction (AEG) is a lethal malignancy originating from the distal esophagus and the esophagogastric junction (1,2). The incidence of AEG has increased rapidly worldwide during the past two decades (3-6). The prognosis of AEG is poor due to distant metastasis at the time of diagnosis and the limited treatment options (7,8). Trastuzumab, a monoclonal antibody targeting human epidermal growth factor receptor 2 (HER2), has emerged as an effective therapeutic option for AEG when combined with chemotherapy (9).In a phase III, open-label, international, randomized controlled trial, Bang et al (9) observed that patients treated with trastuzumab plus chemotherapy had longer median follow-up and median overall survival times compared with patients treated with chemotherapy alone. The authors suggested that trastuzumab in combination with chemotherapy may be a new standard option for the first-line treatment of HER2-positive advanced gastric or gastro-esophageal junction cancer (9). International National Comprehensive Cancer Network Guidelines recommend the detection of HER2 in patients with AEG in order to guide the selection of further clinical treatment options (10). However, trastuzumab treatment is invalid for nearly half of HER2-positive patients (9), and the mechanisms of drug resistance are curre...

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The versatile functions of Sox9 in development, stem cells, and human diseases

Cited by 277 publications

References 142 publications

Loss of DDRGK1 modulates SOX9 ubiquitination in spondyloepimetaphyseal dysplasia

Loss of DDRGK1 modulates SOX9 ubiquitination in spondyloepimetaphyseal dysplasia

The secretome of MUSE cells contains factors that may play a role in regulation of stemness, apoptosis and immunomodulation

Inï¿½vitro study on the role of SOX9 in trastuzumab resistance of adenocarcinoma of the esophagogastric junction

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