SOX2 in development and cancer biology

Novak, Daniel; Hüser, Laura; Elton, Jonathan J.; Umansky, Viktor; Altevogt, Peter; Utikal, Jochen

doi:10.1016/j.semcancer.2019.08.007

Cited by 248 publications

(182 citation statements)

References 138 publications

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“…Substantial evidence suggests that breast cancer initiation and the development of resistance and metastasis are driven by CSCs. The embryonic stem cell factor Sox2, implicated in development, pluripotency, and cancer biology [43], is also found in breast stem/progenitor cells [30] and is highly expressed in breast tumors that have developed resistance to endocrine therapy and display poor clinical outcome [29]. Furthermore, the silencing of the Sox2 gene reduces the size of the stem/progenitor cell population and restores sensitivity to tamoxifen, while the ectopic expression of Sox2 increases the CSC population and leads to reduced therapy sensitivity in vitro and in vivo [29].…”

Section: Discussionmentioning

confidence: 99%

Single-Cell Probe Force Studies to Identify Sox2 Overexpression-Promoted Cell Adhesion in MCF7 Breast Cancer Cells

Iturri

Weber

Vivanco

et al. 2020

Cells

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The replacement of the cantilever tip by a living cell in Atomic Force Microscopy (AFM) experiments permits the direct quantification of cell–substrate and cell–cell adhesion forces. This single-cell probe force measurement technique, when complemented by microscopy, allows controlled manipulation of the cell with defined location at the area of interest. In this work, a setup based on two glass half-slides, a non-fouling one with bacterial S-layer protein SbpA from L. sphaericus CMM 2177 and the second with a fibronectin layer, has been employed to measure the adhesion of MCF7 breast cancer cells to fibronectin films (using SbpA as control) and to other cells (symmetric vs. asymmetric systems). The measurements aimed to characterize and compare the adhesion capacities of parental cells and cells overexpressing the embryonic transcription factor Sox2, which have a higher capacity for invasion and are more resistant to endocrine therapy in vivo. Together with the use of fluorescence techniques (epifluorescence, Total Internal Fluorescence Microscopy (TIRF)), the visualization of vinculin and actin distribution in cells in contact with fibronectin surfaces is enabled, facilitating the monitoring and quantification of the formation of adhesion complexes. These findings demonstrate the strength of this combined approach to assess and compare the adhesion properties of cell lines and to illustrate the heterogeneity of adhesive strength found in breast cancer cells.

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Section: Discussionmentioning

confidence: 99%

Single-Cell Probe Force Studies to Identify Sox2 Overexpression-Promoted Cell Adhesion in MCF7 Breast Cancer Cells

Iturri

Weber

Vivanco

et al. 2020

Cells

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“…The SOX2 amplification or overexpression was found in at least 25 different human cancers, and forced SOX2 expression promotes neoplastic progression by accelerating cancer cell proliferation, migration, invasion, and metastasis. 5 Moreover, elevated SOX2 expression is positively correlated with drug resistance and poor survival of cancer patients. 5,6 Therefore, targeting SOX2 appears to be a very attractive therapeutic avenue for cancer treatment.…”

Section: Introductionmentioning

confidence: 99%

“…5 Moreover, elevated SOX2 expression is positively correlated with drug resistance and poor survival of cancer patients. 5,6 Therefore, targeting SOX2 appears to be a very attractive therapeutic avenue for cancer treatment. 7…”

Section: Introductionmentioning

confidence: 99%

Functional characterization of SOX2 as an anticancer target

Zhang

Xiong

Sun

2020

Sig Transduct Target Ther

138

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SOX2 is a well-characterized pluripotent factor that is essential for stem cell self-renewal, reprogramming, and homeostasis. The cellular levels of SOX2 are precisely regulated by a complicated network at the levels of transcription, post-transcription, and posttranslation. In many types of human cancer, SOX2 is dysregulated due to gene amplification and protein overexpression. SOX2 overexpression is associated with poor survival of cancer patients. Mechanistically, SOX2 promotes proliferation, survival, invasion/ metastasis, cancer stemness, and drug resistance. SOX2 is, therefore, an attractive anticancer target. However, little progress has been made in the efforts to discover SOX2 inhibitors, largely due to undruggable nature of SOX2 as a transcription factor. In this review, we first briefly introduced SOX2 as a transcription factor, its domain structure, normal physiological functions, and its involvement in human cancers. We next discussed its role in embryonic development and stem cell-renewal. We then mainly focused on three aspects of SOX2: (a) the regulatory mechanisms of SOX2, including how SOX2 level is regulated, and how SOX2 cross-talks with multiple signaling pathways to control growth and survival; (b) the role of SOX2 in tumorigenesis and drug resistance; and (c) current drug discovery efforts on targeting SOX2, and the future perspectives to discover specific SOX2 inhibitors for effective cancer therapy.

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“…SOX2, as one of the Yamanaka factors, is involved in the conversion of mouse embryonic fibroblast cells (MEFs) into induced pluripotent stem cells (iPSCs) (Takahashi and Yamanaka, 2006). Recently, SOX2 amplification, usually couples with aberrantly increased expression, were found in various human cancers, including breast, lung, esophagus, colon, prostate, ovarian among the others (Novak et al, 2019). SOX2 overexpression promotes cancer progression by accelerating cell proliferation, colony formation, migration, invasion, and sphere formation.…”

mentioning

confidence: 99%

“…SOX2 overexpression promotes cancer progression by accelerating cell proliferation, colony formation, migration, invasion, and sphere formation. Furthermore, SOX2 is causally related to the development of the resistance of cancer cells to chemotherapy, radiotherapy and targeted therapy in different types of human cancers, likely due to its ability to maintain the stemness of cancer stem cells (CSCs), which are defined as a subpopulation within tumor cells being equipped with stem cell-like properties that survives the treatment and initiates tumor progression (Novak et al, 2019). Thus, SOX2 has been validated as an attractive anticancer target (Huser et al, 2018).…”

mentioning

confidence: 99%