Profiling gene promoter occupancy of Sox2 in two phenotypically distinct breast cancer cell subsets using chromatin immunoprecipitation and genome-wide promoter microarrays

Jung, Karen; Wang, Peng; Gupta, Nidhi; Gopal, Keshav; Wu, Fang; Ye, Xiaoxia; Alshareef, Abdulraheem; Bigras, Gilbert; McMullen, Todd; Abdulkarim, Bassam; Lai, Raymond

doi:10.1186/s13058-014-0470-2

Cited by 14 publications

(26 citation statements)

References 55 publications

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“…The signaling cascade finally activates the anti-apoptotic factor Bcl and the inhibitory apoptotic factors Bad and Bax [25e28]. Furthermore, a recent study showed that Sox2 has the ability to bind the promoter region of ErbB2 [29]. These previous results support our findings that Sox2 promotes SGC survival through ErbB signaling.…”

Section: Discussionsupporting

confidence: 89%

Sox2 promotes survival of satellite glial cells in vitro

Koike

Wakabayashi

Mori

et al. 2015

Biochemical and Biophysical Research Communications

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Sox2 is a transcriptional factor expressed in neural stem cells. It is known that Sox2 regulates cell differentiation, proliferation and survival of the neural stem cells. Our previous study showed that Sox2 is expressed in all satellite glial cells of the adult rat dorsal root ganglion. In this study, to examine the role of Sox2 in satellite glial cells, we establish a satellite glial cell-enriched culture system. Our culture method succeeded in harvesting satellite glial cells with the somata of neurons in the dorsal root ganglion. Using this culture system, Sox2 was downregulated by siRNA against Sox2. The knockdown of Sox2 downregulated ErbB2 and ErbB3 mRNA at 2 and 4 days after siRNA treatment. MAPK phosphorylation, downstream of ErbB, was also inhibited by Sox2 knockdown. Because ErbB2 and ErbB3 are receptors that support the survival of glial cells in the peripheral nervous system, apoptotic cells were also counted. TUNEL-positive cells increased at 5 days after siRNA treatment. These results suggest that Sox2 promotes satellite glial cell survival through the MAPK pathway via ErbB receptors.

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Section: Discussionsupporting

confidence: 89%

Sox2 promotes survival of satellite glial cells in vitro

Koike

Wakabayashi

Mori

et al. 2015

Biochemical and Biophysical Research Communications

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“…Finally, we asked if the dichotomy of RU and RR also exists in primary patient samples. Four cases of fresh, previously untreated TNBC patient samples were processed and infected with the SRR2 reporter using a protocol described previously [ 8 ]. As shown in Figure 4C , we detected a small (1.1 to 3.8%) RR cell subset in all cases examined.…”

Section: Resultsmentioning

confidence: 99%

“…Experimentally, it was demonstrated that enforced expression of Sox2 in breast cancer cells contributes to enhanced proliferation and invasion in vitro , and tumor formation in xenograft mouse models [ 4 , 5 ]. In studies reported by us, we found that the transcriptional activity of Sox2, detectable by the Sox2 regulatory factor-2 (SRR2) reporter, is found only in a small subset of cells in estrogen receptor-positive breast cancer cell lines and patient samples [ 7 , 8 ]. This has since been confirmed in studies by other groups [ 9 , 10 ].…”

Section: Introductionmentioning

confidence: 99%

Triple negative breast cancers comprise a highly tumorigenic cell subpopulation detectable by its high responsiveness to a Sox2 regulatory region 2 (SRR2) reporter

et al. 2015

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We have recently described a novel phenotypic dichotomy within estrogen receptor-positive breast cancer cells; the cell subset responsive to a Sox2 regulatory region (SRR2) reporter (RR cells) are significantly more tumorigenic than the reporter unresponsive (RU) cells. Here, we report that a similar phenomenon also exists in triple negative breast cancer (TNBC), with RR cells more tumorigenic than RU cells. First, examination of all 3 TNBC cell lines stably infected with the SRR2 reporter revealed the presence of a cell subset exhibiting reporter activity. Second, RU and RR cells purified by flow cytometry showed that RR cells expressed higher levels of CD44, generated more spheres in a limiting dilution mammosphere formation assay, and formed larger and more complex structures in Matrigel. Third, within the CD44High/CD24− tumor-initiating cell population derived from MDA-MB-231, RR cells were significantly more tumorigenic than RU cells in an in vivo SCID/Beige xenograft mouse model. Examination of 4 TNBC tumors from patients also revealed the presence of a RR cell subset, ranging from 1.1-3.8%. To conclude, we described a novel phenotypic heterogeneity within TNBC, and the SRR2 reporter responsiveness is a useful marker for identifying a highly tumorigenic cell subset within the CD44High/CD24−tumor-initiating cell population.

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“…CD133 and ALDH1) that change rapidly in response to cellular conditions are used to isolate cancer stem cells. To illustrate this point, we focus on CD133, which has been linked with SOX2 expression and cancer stem cells in many tumor cell types [ 85 – 91 ]. In 2003, CD133 was reported to serve as a marker for the tumor-initiating cells of brain tumors.…”

Section: Expression and Function Of Sox2 In Cancermentioning

confidence: 99%

The dark side of SOX2: cancer - a comprehensive overview

Wuebben

Rizzino²

2017

Oncotarget

185

161

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The pluripotency-associated transcription factor SOX2 is essential during mammalian embryogenesis and later in life, but SOX2 expression can also be highly detrimental. Over the past 10 years, SOX2 has been shown to be expressed in at least 25 different cancers. This review provides a comprehensive overview of the roles of SOX2 in cancer and focuses on two broad topics. The first delves into the expression and function of SOX2 in cancer focusing on the connection between SOX2 levels and tumor grade as well as patient survival. As part of this discussion, we address the developing connection between SOX2 expression and tumor drug resistance. We also call attention to an under-appreciated property of SOX2, its levels in actively proliferating tumor cells appear to be optimized to maximize tumor growth - too little or too much SOX2 dramatically alters tumor growth. The second topic of this review focuses on the exquisite array of molecular mechanisms that control the expression and transcriptional activity of SOX2. In addition to its complex regulation at the transcriptional level, SOX2 expression and activity are controlled carefully by microRNAs, long non-coding RNAs, and post-translational modifications. In the Conclusion and Future Perspectives section, we point out that there are still important unanswered questions. Addressing these questions is expected to lead to new insights into the functions of SOX2 in cancer, which will help design novels strategies for more effectively treating some of the most deadly cancers.

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Profiling gene promoter occupancy of Sox2 in two phenotypically distinct breast cancer cell subsets using chromatin immunoprecipitation and genome-wide promoter microarrays

Cited by 14 publications

References 55 publications

Sox2 promotes survival of satellite glial cells in vitro

Sox2 promotes survival of satellite glial cells in vitro

Triple negative breast cancers comprise a highly tumorigenic cell subpopulation detectable by its high responsiveness to a Sox2 regulatory region 2 (SRR2) reporter

The dark side of SOX2: cancer - a comprehensive overview

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