Therapeutic relevance of SOX9 stem cell factor in gastric cancer

Carrasco‐García, Estefanía; Álvarez-Satta, María; García-Puga, Mikel; Ribeiro, Marcelo Lima; Arévalo, Sara; Araúzo‐Bravo, Marcos J.; Matheu, Ander

doi:10.1080/14728222.2019.1559826

Cited by 15 publications

(11 citation statements)

References 64 publications

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“…Several studies have reported high levels of SOX9 in gastric cancer [25–29], but the association with patient prognosis is poorly defined. One study reported a significant association between high SOX9 expression, advanced TNM stages, and lower overall survival [30], further reviewed in [31]. On the other hand, Sun et al [28] reported that SOX9 expression was decreased in tumours due to promoter methylation and inversely related to the advanced tumour stage, vessel infiltration, and nodal metastasis, but did not associate with patient overall survival.…”

Section: Introductionmentioning

confidence: 99%

Expression and Clinical Relevance of SOX9 in Gastric Cancer

et al. 2019

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Gastric cancer is one of the most frequent tumours and the third leading cause of cancer-related death worldwide. The investigation of new biomarkers that can predict patient outcome more accurately and allow better treatment and follow-up decisions is of crucial importance. SOX9 (sex-determining region Y (SRY)-box 9) is a regulator of cell fate decisions in embryogenesis and adulthood. Here, we sought to ascertain the relevance of SOX9 transcription factor as a prognostic marker in gastric cancer. SOX9 expression was analyzed by immunohistochemistry in 333 gastric adenocarcinoma cases, and its association with clinicopathological and follow-up data was evaluated. SOX9 nuclear expression was absent in 17% of gastric cancer cases and predicted worse disease-free survival (P=0.03). SOX9 expression was associated with lower risk of relapse in Cox univariable analysis (HR=0.58; 95% CI=0.35-0.97; P=0.04). The prognostic value of SOX9 was more pronounced in tumours with expansive growth (P=0.01) or with venous invasion (P=0.02). Two validation cohorts from the Cancer Genome Atlas (TCGA) and the Asian Cancer Research Group (ACRG) confirmed that low SOX9 expression was significantly associated with poor patient outcome. In conclusion, we have identified SOX9 as a biomarker of disease relapse in gastric cancer patients. Further experiments are needed to elucidate its biological relevance at the cellular level.

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Section: Introductionmentioning

confidence: 99%

Expression and Clinical Relevance of SOX9 in Gastric Cancer

et al. 2019

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“…The competence for TEAD1 binding was assessed by a luciferase reporter system as SOX2 and SOX9 have been described as a relevant regulator of the population of GCSCs. 37 , 38 The dual‐luciferase results show that shYAP reduced the SOX2 and SOX9 promoter activity (Figure S2 C). In addition, decreased SOX2 and SOX9 expression has been shown to be related to TAK1 interfered expression (Figure 6A ).…”

Section: Resultsmentioning

confidence: 96%

The stabilization of yes‐associated protein by TGFβ‐activated kinase 1 regulates the self‐renewal and oncogenesis of gastric cancer stem cells

Wang

Sun

Zhu

et al. 2021

J Cellular Molecular Medi

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“…39 SOX9 has been well established as a dispensable transcription factor regulating many developmental signaling pathways, and its aberrant expression has been was associated with tumor initiation, proliferation, metastasis, and stem cell maintenance. 40,41 This is also true for EC, since SOX9 has been reported as an independent risk factor of endometrial gland hyperplasia in uterine epithelia, which is a precursor of EC. 42 In addition, overexpression of SOX9 was found to trigger proliferation of EC cells.…”

Section: Discussionmentioning

confidence: 91%

“…This was partially in line with a previous study which reported that miR‐105 suppressed epithelial‐mesenchymal transition and metastasis of gastric cancers by targeting SOX9 39 . SOX9 has been well established as a dispensable transcription factor regulating many developmental signaling pathways, and its aberrant expression has been was associated with tumor initiation, proliferation, metastasis, and stem cell maintenance 40,41 . This is also true for EC, since SOX9 has been reported as an independent risk factor of endometrial gland hyperplasia in uterine epithelia, which is a precursor of EC 42 .…”

Section: Discussionmentioning

confidence: 98%

Circ_0109046 promotes the malignancy of endometrial carcinoma cells through the microRNA‐105/SOX9/Wnt/β‐catenin axis

Liu

Piao

et al. 2020

IUBMB Life

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Emerging evidence suggests the important involvements of circular RNAs (cir-cRNAs) in cancer progression. This study focuses on the function of Circ_0109046 on the malignancy of endometrial carcinoma (EC) cells and the molecules involved. First, high expression of Circ_0109046 was found in EC tissues compared to the adjacent tissues, and it predicted unfavorable prognosis in patients. Similarly, high expression of Circ_0109046 was confirmed in EC cells relative to that in normal endometrial epithelial cells. Silencing of Circ_0109046 in AN3-CA cells inhibited proliferation and aggressiveness but increased apoptosis of cells. Circ_0109046 was mainly sub-localized in cytoplasm, and it mediated SOX9 expression through sponging microRNA (miR)-105. The proliferation and aggressiveness of EC cells suppressed by Circ_0109046 downregulation was recovered upon SOX9 overexpression. SOX9 activated the Wnt/β-catenin pathway. Furthermore, downregulation of Circ_0109046 reduced the growth of xenograft tumors in nude mice. This study evidenced that Circ_0109046 upregulates SOX9 expression through sponging miR105, leading to activation of Wnt/β-catenin signaling and the malignant growth of EC. This study may offer novel understanding in EC treatment.

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Therapeutic relevance of SOX9 stem cell factor in gastric cancer

Cited by 15 publications

References 64 publications

Expression and Clinical Relevance of SOX9 in Gastric Cancer

Expression and Clinical Relevance of SOX9 in Gastric Cancer

The stabilization of yes‐associated protein by TGFβ‐activated kinase 1 regulates the self‐renewal and oncogenesis of gastric cancer stem cells

Circ_0109046 promotes the malignancy of endometrial carcinoma cells through the microRNA‐105/SOX9/Wnt/β‐catenin axis

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