SOX6 is downregulated in osteosarcoma and suppresses the migration, invasion and epithelial-mesenchymal transition via TWIST1 regulation

Wang, Zheng; Li, Junjie; Li, Kun; Xu, Jianjun

doi:10.3892/mmr.2018.8681

Cited by 16 publications

(21 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In pancreatic cancer, Sox6 was downregulated in patients with metastatic disease, and its overexpression could suppress tumor invasiveness by inhibiting EMT 22 . Similar findings were also observed in osteosarcoma 24 . In contrast, for some types of brain tumors, 20,40 SOX6 expression was higher compared with normal tissues, and high expression of SOX6 might be a potential diagnostic marker.…”

Section: Discussionsupporting

confidence: 59%

“…In addition, several studies also indicated SOX6 could suppress the migration and invasion of cancer cells. In pancreatic cancer 22 and osteosarcoma, 24 SOX6 was reported to influence EMT via the regulation of Twist1 through the recruitment of HDAC1 to the promoter of the Twist1 gene. These findings suggested that SOX6 was involved in the regulation of processes involved in cancer biology and could regulate different target genes during the development of different types of cancer.…”

Section: Discussionmentioning

confidence: 99%

“…The D group has attracted intensive attention and has been recently recognized as an important transcriptional regulator associated with several types of cancer 19 . SOX6, a main representative of D group, is involved in the regulation of carcinogenesis in various human malignancies, such as glioma, 20 esophageal squamous cell carcinoma, 21 pancreatic cancer, 22 hepatocellular carcinoma, 23 osteosarcoma, 24 lung adenocarcinoma, 25 ovarian cancer, 26 and leukemia 27 . However, the role of SOX6 in ccRCC development remains unclear.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

SOX6 represses tumor growth of clear cell renal cell carcinoma by HMG domain‐dependent regulation of Wnt/β‐catenin signaling

Chen

Xie

et al. 2020

Molecular Carcinogenesis

View full text Add to dashboard Cite

Sex‐determining region Y box (SOXs) are expressed in various cells and control cell fate and differentiation in a multitude of physiologic processes. SOX6, a main representative of SOXs, is involved in the regulation of carcinogenesis in various human malignancies. However, the role of SOX6 in clear cell renal cell carcinoma (ccRCC) remains unclear. In this study, SOX6 expression in ccRCC and its clinical significance were investigated. In vitro and in vivo assays were used to explore the tumor‐related function and the underlying molecular mechanism of SOX6 in ccRCC. We confirmed that SOX6 was frequently downregulated in ccRCC tissues and cell lines. Besides, downregulation of SOX6 was significantly associated with larger tumor sizes, advanced tumor stage, higher Fuhrman grades, and its expression could act as an independent prognostic factor for ccRCC (hazards ratio = 0.590, P = .026). Gain/loss‐of‐function experiments demonstrated that SOX6 could remarkably inhibit tumor cell growth and foci formation in vitro and xenograft tumorigenesis in vivo, respectively. Mechanistically, SOX6 could influence cell cycle by regulating the G1/the S phase transition and had an inhibitory effect on Wnt/β‐catenin signaling as well as its target genes, c‐Myc and cyclin D1. Interesting, the tumor‐suppressive function of SOX6 was proved to be dependent on its specific high‐mobility‐group (HMG) domain. In general, our findings indicated that SOX6 was a novel tumor suppressor and prognostic biomarker in ccRCC. SOX6 could inhibit tumor growth by negatively regulating the Wnt/β‐catenin signaling pathway in an HMG domain‐dependent manner in ccRCC, which might provide a novel therapeutic approach for ccRCC.

show abstract

Section: Discussionsupporting

confidence: 59%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

SOX6 represses tumor growth of clear cell renal cell carcinoma by HMG domain‐dependent regulation of Wnt/β‐catenin signaling

Chen

Xie

et al. 2020

Molecular Carcinogenesis

View full text Add to dashboard Cite

show abstract

“…SOX6 is aberrantly upregulated in numerous types of cancer, including pancreatic cancer (37), prostate cancer (38), ovarian cancer (29), colorectal cancer (39) and hepatocellular carcinoma (40). SOX6 may contribute to the occurrence and development of tumorigenesis and tumor development through the regulation of various biological features, including cell proliferation, cycle, apoptosis, epithelial-mesenchymal transition and metastasis (28)(29)(30). The current study demonstrated that miR-765 directly targets SOX6 to implicate the progression of MM.…”

Section: Discussionmentioning

confidence: 59%

“…3A). SOX6 was selected for further experimental validation as SOX6 is involved in the tumorigenesis and tumor development of multiple types of human cancer (28)(29)(30). A luciferase reporter assay was performed to confirm whether miR-765 directly targets the 3'-UTR of SOX6.…”

Section: Sox6 Is a Direct Target Gene Of Mir-765 In MM Cellsmentioning

confidence: 99%

microRNA‑765 is pregulated in multiple myeloma and serves an oncogenic role by directly targeting SOX6

Long

et al. 2019

Exp Ther Med

View full text Add to dashboard Cite

Increasing evidence has revealed that microRNAs (miRNAs) are closely associated with multiple myeloma (MM) pathogenesis and progression. Therefore, an in-depth understanding of the biological functions of miRNAs in MM may be helpful for the identification of promising therapeutic techniques for patients with MM. miRNA-765 (miR-765) has been reported to be dysregulated in many types of human cancer. However, the expression pattern, specific roles and underlying mechanisms of miR-765 in MM remain largely unknown. In the present study, plasma miR-765 significantly increased in patients with MM and cell lines. The downregulation of miR-765 in MM cells attenuated proliferation and promoted apoptosis. Bioinformatics analysis predicted that SRY-Box 6 (SOX6) was a putative target of miR-765. This was experimentally verified using a luciferase reporter assay, reverse transcription-quantitative PCR and western blot analysis. Furthermore, plasma SOX6 was downregulated in patients with MM and the downregulation of SOX6 was inversely correlated with that of miR-765 expression. Furthermore, SOX6 knockdown markedly abrogated the effects of miR-765 underexpression on cell proliferation and apoptosis in MM. The current study demonstrated that miR-765 serves an oncogenic role in MM progression by directly targeting SOX6, suggesting that miR-765 may be a potential therapeutic target for MM prevention and treatment.

show abstract

MAP4K4 and WT1 mediate SOX6‐induced cellular senescence by synergistically activating the ATF2–TGFβ2–Smad2/3 signaling pathway in cervical cancer

Zheng,

Liu,

Shi

et al. 2024

Molecular Oncology

View full text Add to dashboard Cite

SRY‐box transcription factor 6 (SOX6) is a member of the SOX gene family and inhibits the proliferation of cervical cancer cells by inducing cell cycle arrest. However, the final cell fate and significance of these cell‐cycle‐arrested cervical cancer cells induced by SOX6 remains unclear. Here, we report that SOX6 inhibits the proliferation of cervical cancer cells by inducing cellular senescence, which is mainly mediated by promoting transforming growth factor beta 2 (TGFB2) gene expression and subsequently activating the TGFβ2–Smad2/3–p53–p21WAF1/CIP1–Rb pathway. SOX6 promotes TGFB2 gene expression through the MAP4K4–MAPK (JNK/ERK/p38)–ATF2 and WT1–ATF2 pathways, which is dependent on its high‐mobility group (HMG) domain. In addition, the SOX6‐induced senescent cervical cancer cells are resistant to cisplatin treatment. ABT‐263 (navitoclax) and ABT‐199 (venetoclax), two classic senolytics, can specifically eliminate the SOX6‐induced senescent cervical cancer cells, and thus significantly improve the chemosensitivity of cisplatin‐resistant cervical cancer cells. This study uncovers that the MAP4K4/WT1–ATF2–TGFβ2 axis mediates SOX6‐induced cellular senescence, which is a promising therapeutic target in improving the chemosensitivity of cervical cancer.

show abstract

SOX6 is downregulated in osteosarcoma and suppresses the migration, invasion and epithelial-mesenchymal transition via TWIST1 regulation

Cited by 16 publications

References 32 publications

SOX6 represses tumor growth of clear cell renal cell carcinoma by HMG domain‐dependent regulation of Wnt/β‐catenin signaling

SOX6 represses tumor growth of clear cell renal cell carcinoma by HMG domain‐dependent regulation of Wnt/β‐catenin signaling

microRNA‑765 is pregulated in multiple myeloma and serves an oncogenic role by directly targeting SOX6

MAP4K4 and WT1 mediate SOX6‐induced cellular senescence by synergistically activating the ATF2–TGFβ2–Smad2/3 signaling pathway in cervical cancer

Contact Info

Product

Resources

About