SOX9: The master regulator of cell fate in breast cancer

Jana, Sumit Kumar; Krishna, B. Madhu; Singhal, Jyotsana; Horne, David; Awasthi, Yogesh C.; Salgia, Ravi; Singhal, Sharad S.

doi:10.1016/j.bcp.2019.113789

Cited by 56 publications

(49 citation statements)

References 131 publications

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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: 90%

“…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%

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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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Section: Discussionmentioning

confidence: 90%

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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“…SOX9 is a pivotal modulator of stemness and contributes to cancer development ( 17 ). To explore the relevance of SOX9 in TNBC, SOX9 expression was detected in BT-549, MDA-MB-231, MDA-MB-436 and MDA-MB-468 cells.…”

Section: Resultsmentioning

confidence: 99%

“…TNBC is a malignant tumor with a high metastasis rate ( 19 ). It has been reported that SOX9 contributes to the migration and invasion of various cancer cells ( 17 , 20 , 21 ). Therefore, the present study explored whether SOX9-knockdown regulated the migration of TNBC cells using wound-healing assays.…”

Section: Resultsmentioning

confidence: 99%

Downregulation of SOX9 suppresses breast cancer cell proliferation and migration by regulating apoptosis and cell cycle arrest

Wang¹,

Dang²,

Luo³

et al. 2021

Oncol Lett

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SRY-related high-mobility group box 9 (SOX9) is an important transcriptional factor that regulates diverse genes involved in development and stemness. Dysregulation of SOX9 encourages carcinogenesis in various types of cancer, including breast cancer. The present study aimed to explore the role of SOX9 in triple-negative breast cancer (TNBC). SOX9 expression was significantly upregulated in the TNBC MDA-MB-231, MDA-MB-436 and MDA-MB-468 cell lines compared with that in BT-549 cells. Based on a lentivirus assay, SOX9 inhibition in MDA-MB-231 and MDA-MB-436 cells suppressed cell proliferation and colony formation. Apoptosis was increased and the cell cycle was arrested at the G 0 /G 1 phase in SOX9-knockdown cells. Transwell and wound-healing assays demonstrated that SOX9 inhibition decreased the migration and invasion of MDA-MB-231 and MDA-MB-436 cells. RNA sequencing identified that numerous genes were regulated by SOX9, including nucleophosmin, thioredoxin reductase 1, succinate dehydrogenase complex subunit D, nuclear receptor binding SET domain protein 2, eukaryotic translation initiation factor 4γ1 and glycogen phosphorylase L. Overall, the current study suggested that SOX9 acted as an oncogene in TNBC.

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“…RIP140 expression could therefore be used as a marker for the identification of patients who might benefit from personalized anticancer therapies based on a SOX9 targeting by specific inhibitors or compounds that attenuate its expression [54]. Moreover, it would be interesting to investigate whether the same cross-talk between SOX9 and RIP140 also occurs in other types of cancer, including breast cancer [55].…”

Section: Discussionmentioning

confidence: 99%

RIP140 Represses Intestinal Paneth Cell Differentiation and Interplays with SOX9 Signaling in Colorectal Cancer

Gleizes

Triki

Bonnet

et al. 2021

Cancers

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RIP140 is a major transcriptional coregulator of gut homeostasis and tumorigenesis through the regulation of Wnt/APC signaling. Here, we investigated the effect of RIP140 on Paneth cell differentiation and its interplay with the transcription factor SOX9. Using loss of function mouse models, human colon cancer cells, and tumor microarray data sets we evaluated the role of RIP140 in SOX9 expression and activity using RT-qPCR, immunohistochemistry, luciferase reporter assays, and GST-pull down. We first evidence that RIP140 strongly represses the Paneth cell lineage in the intestinal epithelium cells by inhibiting Sox9 expression. We then demonstrate that RIP140 interacts with SOX9 and inhibits its transcriptional activity. Our results reveal that the Wnt signaling pathway exerts an opposite regulation on SOX9 and RIP140. Finally, the levels of expression of RIP140 and SOX9 exhibit a reverse response and prognosis value in human colorectal cancer biopsies. This work highlights an intimate transcriptional cross-talk between RIP140 and SOX9 in intestinal physiopathology.

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SOX9: The master regulator of cell fate in breast cancer

Cited by 56 publications

References 131 publications

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

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

Downregulation of SOX9 suppresses breast cancer cell proliferation and migration by regulating apoptosis and cell cycle arrest

RIP140 Represses Intestinal Paneth Cell Differentiation and Interplays with SOX9 Signaling in Colorectal Cancer

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