SOX2 function and Hedgehog signaling pathway are co-conspirators in promoting androgen independent prostate cancer

Kar, Swayamsiddha; Sengupta, Dipta; Deb, Moonmoon; Pradhan, Nibedita; Patra, Samir Kumar

doi:10.1016/j.bbadis.2016.11.001

Cited by 26 publications

(14 citation statements)

References 49 publications

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“…Here we found that OKC expresses SOX2 and BCL-2 proteins in a significant manner, but with no statistical correlation between them. Nevertheless, it is plausible to assume that their expression in OKC is not just a coincidence, since both are related to the Hh signaling pathway (35,39,40) and both seem to be influenced by miR-15a (24,41). Our findings are in sync with those of other studies that also found SOX2 and BCL-2 expression in OKC (9,18).…”

Section: Discussionsupporting

confidence: 89%

SOX2 and BCL-2 Expressions in Odontogenic Keratocyst and Ameloblastoma

Silva¹,

Silva²,

Lima³

et al. 2020

Med Oral

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Background: The purpose of this experimental study was to compare the immunohistochemical expression of SOX2 and BCL-2 in Odontogenic Keratocyst (OKC) and Ameloblastoma (AB) specimens, and to identify a possible correlation in their expression. Material and Methods: Immunohistochemical analysis was performed to evaluate SOX2 and BCL-2 expression in OKC (n = 20) and AB (n = 20). The immunoexpression was analyzed by a quantitative and qualitative scoring system. The comparison between the immunoexpression of SOX 2 and BCL-2 was assessed by the Mann-Whitney U-test. Spearman's correlation coefficient evaluated the correlation between SOX2 and BCL-2 expressions. Results: SOX2 and BCL-2 expression was observed in all specimens of OKC in the full thickness of the epithelium lining. SOX2 immunostaining was higher in OKC, in comparison with AB samples (P<0.05). BCL-2 immunostaining between OKC and AB was not statistically significant. There was no significant correlation between SOX2 and BCL-2 in OKC and AB specimens. Conclusions: SOX2 and BCL-2 expressions in OKC may suggest their relationship with the biological behavior of this lesion, and the higher expression of SOX2 might be an upstream influence on the Hh signaling pathway.

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Section: Discussionsupporting

confidence: 89%

SOX2 and BCL-2 Expressions in Odontogenic Keratocyst and Ameloblastoma

Silva¹,

Silva²,

Lima³

et al. 2020

Med Oral

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“…It is possible that more than 1 signaling pathway is active in a particular cancer; therefore, simultaneously targeting these pathways may help prevent or postpone the development of resistance. For example, in vitro in prostate cancer cells, inhibition of HH and Sox2 signaling concomitantly led to reduced metastatic behavior, survival capacity and invasiveness, and increased apoptosis [90]. In a mouse model of medulloblastoma, blocking mammalian target of rapamycin (mTOR) and HH signaling prevented HHI resistance [86].…”

Section: The Role Of Multiple Signaling Pathwaysmentioning

confidence: 99%

Hedgehog signaling inhibitors in solid and hematological cancers

Cortes

Gutzmer

Kieran

et al. 2019

Cancer Treatment Reviews

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Background: The hedgehog signaling pathway is normally tightly regulated. Mutations in hedgehog pathway components may lead to abnormal activation. Aberrantly activated hedgehog signaling plays a major role in the development of solid and hematological cancer. In recent years, inhibitors have been developed that attenuate hedgehog signaling; 2 have been approved for use in basal cell carcinoma (BCC), while others are under development or in clinical trials. The aim of this review is to provide an overview of known hedgehog inhibitors (HHIs) and their potential for the treatment of hematological cancers and solid tumors beyond BCC. Design: Published literature was searched to identify articles relating to HHIs in noncutaneous cancer. Both preclinical and clinical research articles were included. In addition, relevant clinical trial results were identified from www.clinicaltrials.gov. Information on the pharmacology of HHIs is also included. Results: HHIs show activity in a variety of solid and hematological cancers. In preclinical studies, HHIs demonstrated efficacy in pancreatic cancer, rhabdomyosarcoma, breast cancer, and acute myeloid leukemia (AML). In clinical studies, HHIs showed activity in medulloblastoma, as well as prostate, pancreatic, and hematological cancers. Current clinical trials testing the efficacy of HHIs are underway for prostate, pancreatic, and breast cancers, as well as multiple myeloma and AML. Conclusions: As clinical trial results become available, it will be possible to discern which additional tumor types are suited to HHI mono-or combination therapy with other anticancer agents. The latter strategy may be useful for delaying or overcoming drug resistance. Dysregulated hedgehog signaling and the development of cancer The HH signaling pathway is normally tightly regulated; however, dysregulation due to mutations in Smo or Ptch1 plays a major role in

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“…Furthermore, mutations in TP53 and RB1 tumor suppressor genes can promote a cellular plasticity state mediated by increased expression of SOX2 that, when it is compromised with antiandrogen therapy promotes resistance through lineage switching [ 62 ••]. It has also recently been shown that the Hedgehog (HH) signaling pathway and SOX2 co-operate in androgen-independent prostate cancer to promote carcinogenesis [ 146 ].…”

Section: Oncogenic Pathways Involved In Epigenetic Regulationsmentioning

confidence: 99%

Epigenetic Regulation in Prostate Cancer Progression

et al. 2018

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Purpose of ReviewAn important number of newly identified molecular alterations in prostate cancer affect gene encoding master regulators of chromatin biology epigenetic regulation. This review will provide an updated view of the key epigenetic mechanisms underlying prostate cancer progression, therapy resistance, and potential actionable mechanisms and biomarkers.Recent FindingsKey players in chromatin biology and epigenetic master regulators has been recently described to be crucially altered in metastatic CRPC and tumors that progress to AR independency. As such, epigenetic dysregulation represents a driving mechanism in the reprograming of prostate cancer cells as they lose AR-imposed identity.SummaryChromatin integrity and accessibility for transcriptional regulation are key features altered in cancer progression, and particularly relevant in nuclear hormone receptor-driven tumors like prostate cancer. Understanding how chromatin remodeling dictates prostate development and how its deregulation contributes to prostate cancer onset and progression may improve risk stratification and treatment selection for prostate cancer patients.

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SOX2 function and Hedgehog signaling pathway are co-conspirators in promoting androgen independent prostate cancer

Cited by 26 publications

References 49 publications

SOX2 and BCL-2 Expressions in Odontogenic Keratocyst and Ameloblastoma

SOX2 and BCL-2 Expressions in Odontogenic Keratocyst and Ameloblastoma

Hedgehog signaling inhibitors in solid and hematological cancers

Epigenetic Regulation in Prostate Cancer Progression

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