<scp>TGF</scp>‐<i>β</i> induces <scp>SOX</scp>2 expression in a time‐dependent manner in human melanoma cells

Weina, Kasia; Wu, Huizi; Knappe, Nathalie; Orouji, Elias; Novak, Daniel; Bernhardt, Mathias; Hüser, Laura; Larribère, Lionel; Umansky, Viktor; Gebhardt, Christoffer; Utikal, Jochen

doi:10.1111/pcmr.12483

Cited by 29 publications

(23 citation statements)

References 23 publications

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“…Instead, SOX2 knockdown cells displayed reduced invasiveness, whereas SOX2 overexpression increased the invasion capacity of human melanoma cells 23 . In agreement with this, SOX2 was recently shown to mediate TGF-induced invasion in human melanoma cells 24 . Thus, at least in isolated melanoma cells, SOX2 has been implicated in either growth control or invasiveness, but its function in vivo remains to be elucidated.…”

Section: Introductionsupporting

confidence: 61%

“…Of note, studies performed solely in vitro or in combination with xenotransplantation assays provided controversial results, either implicating SOX2 in melanoma cell proliferation or invasion, or also failing to reveal a crucial role in melanoma as in our experiments performed with CRISPR-Cas-mediated knock out cells [20][21][22][23][24] . While the discrepancies between our work and previously published data could potentially be explained by different experimental settings 37 , they could also reflect the heterogeneity of melanoma and, thus, leave open whether SOX2 might fulfill a role in some cases of human melanoma.…”

Section: Sox2 Is Dispensable For Primary Tumor and Metastasis Formationmentioning

confidence: 99%

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Sox2 is dispensable for primary melanoma and metastasis formation

et al. 2017

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Tumor initiation and metastasis formation in many cancers have been associated with emergence of a gene expression program normally active in embryonic or organ-specific stem cells. In particular, the stem cell transcription factor Sox2 is not only expressed in a variety of tumors, but is also required for their formation. Melanoma, the most aggressive skin tumor, derives from melanocytes that during development originate from neural crest stem cells. While neural crest stem cells do not express Sox2, expression of this transcription factor has been reported in melanoma. However, the role of Sox2 in melanoma is controversial. To study the requirement of Sox2 for melanoma formation, we therefore performed CRISPR-Cas9-mediated gene inactivation in human melanoma cells. In addition, we conditionally inactivated Sox2 in a genetically engineered mouse model, in which melanoma spontaneously develops in the context of an intact stroma and immune system. Surprisingly, in both models, loss of Sox2 did neither affect melanoma initiation, nor growth, nor metastasis formation. The lack of a tumorigenic role of Sox2 in melanoma might reflect a distinct stem cell program active in neural crest stem cells and during melanoma formation.

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Section: Introductionsupporting

confidence: 61%

Section: Sox2 Is Dispensable For Primary Tumor and Metastasis Formationmentioning

confidence: 99%

Sox2 is dispensable for primary melanoma and metastasis formation

et al. 2017

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“…SOX genes have been demonstrated to be associated with the differentiation and proliferation of cells (30), and have oncogene functions (31,32). It is reported that SOX10 and SOX1 are tumor-associated antigens of melanoma and small cell lung cancer cells, respectively (33,34).…”

Section: Discussionmentioning

confidence: 99%

MicroRNA‑138 inhibits SOX12 expression and the proliferation, invasion and migration of ovarian cancer cells

Zhu

Jin

2018

Exp Ther Med

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The aim of the present study was to investigate the expression and biological functions of microRNA (miR)-138 in ovarian cancer at the tissue and cellular levels, as well as its underlying mechanisms. A total of 47 patients with ovarian cancer were included in the present study. Ovarian cancer tissues were subjected to staging classification according to the FIGO 2000 criteria. Lymphatic metastasis was also examined. Ovarian cancer A2780 cells were transfected using liposomes. Reverse transcription-quantitative polymerase chain reaction was used to measure the expression of miR-138. A Cell-Counting Kit 8 assay was used to examine cell viability, while a Transwell assay was employed to study cell invasion and migration. The effects of miR-138 on SOX12 protein expression were examined by western blot analysis. A dual luciferase reporter assay was performed to identify the direct interaction between miR-138 and SOX12 gene. Expression of miR-138 was downregulated in ovarian cancer tissues. The level of miR-138 in patients with ovarian cancer with lymphatic metastasis was significantly lower compared with patients without lymphatic metastasis. However, expression of miR-138 was not associated with the stage of ovarian cancer. Upregulation of miR-138 inhibited the proliferation and suppressed the invasion and migration of A2780 cells. SOX12 promoted the proliferation, invasion and migration of A2780 cells. In addition, miR-138 downregulated the expression of SOX12 via binding with the 3′-UTR of SOX12 gene. The present study demonstrates that miR-138 expression is downregulated in ovarian cancer tissues and miR-138 acts as a tumor suppressor gene by inhibiting SOX12 expression and the proliferation, invasion and migration of ovarian cancer cells.

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“…Furthermore, dedifferentiation of melanoma cells is assumed to enhance their malignant potential (Landsberg et al., 2012). Expression of single stem cell factors such as OCT4 or SOX2 increases melanoma stem cell properties, leading to a more aggressive tumor phenotype (Kumar et al., 2012, Santini et al., 2014, Weina et al., 2016). In contrast, the simultaneous expression of three pluripotency markers leading to a semi-stable pluripotent state reduces the tumor-initiating potential.…”

Section: Discussionmentioning

confidence: 99%

Melanoma-Derived iPCCs Show Differential Tumorigenicity and Therapy Response

et al. 2017

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SummaryA point mutation in the BRAF gene, leading to a constitutively active form of the protein, is present in 45%–60% of patients and acts as a key driver in melanoma. Shortly after therapy induction, resistance to MAPK pathway-specific inhibitors develops, indicating that pathway inhibition is circumvented by epigenetic mechanisms. Here, we mimicked epigenetic modifications in melanoma cells by reprogramming them into metastable induced pluripotent cancer cells (iPCCs) with the ability to terminally differentiate into non-tumorigenic lineages. iPCCs and their differentiated progeny were characterized by an increased resistance against targeted therapies, although the cells harbor the same oncogenic mutations and signaling activity as the parental melanoma cells. Furthermore, induction of a pluripotent state allowed the melanoma-derived cells to acquire a non-tumorigenic cell fate, further suggesting that tumorigenicity is influenced by the cell state.

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TGF‐β induces SOX2 expression in a time‐dependent manner in human melanoma cells

Cited by 29 publications

References 23 publications

Sox2 is dispensable for primary melanoma and metastasis formation

Sox2 is dispensable for primary melanoma and metastasis formation

MicroRNA‑138 inhibits SOX12 expression and the proliferation, invasion and migration of ovarian cancer cells

Melanoma-Derived iPCCs Show Differential Tumorigenicity and Therapy Response

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