Role of Sonic Hedgehog (Shh) Signaling in Bladder Cancer Stemness and Tumorigenesis

Syed, Islam S.; Akbari, Pedram; Farhat, Walid A.

doi:10.1007/s11934-015-0568-9

Cited by 30 publications

(27 citation statements)

References 57 publications

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“…The sonic hedgehog signaling pathway (Shh) has emerged as a critical component of organ development and differentiation during embryonic development. However, upon aberrant activation, it triggers cancer initiation and progression, and resistance to chemotherapy [94,95]. Activation of Shh promoted EMT (through the decreased expression of E-cadherin and ZO-1 and the increased expression of N-cadherin) and subsequently increased invasion, clonogenicity, tumorigenicity, and stemness in BC [70].…”

Section: Hedgehog Signaling Pathwaymentioning

confidence: 99%

Emerging Roles of Cancer Stem Cells in Bladder Cancer Progression, Tumorigenesis, and Resistance to Chemotherapy: A Potential Therapeutic Target for Bladder Cancer

Abugomaa

Elbadawy

Yamawaki

et al. 2020

Cells

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Bladder cancer (BC) is a complex and highly heterogeneous stem cell disease associated with high morbidity and mortality rates if it is not treated properly. Early diagnosis with personalized therapy and regular follow-up are the keys to a successful outcome. Cancer stem cells (CSCs) are the leading power behind tumor growth, with the ability of self-renewal, metastasis, and resistance to conventional chemotherapy. The fast-developing CSC field with robust genome-wide screening methods has found a platform for establishing more reliable therapies to target tumor-initiating cell populations. However, the high heterogeneity of the CSCs in BC disease remains a large issue. Therefore, in the present review, we discuss the various types of bladder CSC heterogeneity, important regulatory pathways, roles in tumor progression and tumorigenesis, and the experimental culture models. Finally, we describe the current stem cell-based therapies for BC disease.

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Section: Hedgehog Signaling Pathwaymentioning

confidence: 99%

Emerging Roles of Cancer Stem Cells in Bladder Cancer Progression, Tumorigenesis, and Resistance to Chemotherapy: A Potential Therapeutic Target for Bladder Cancer

Abugomaa

Elbadawy

Yamawaki

et al. 2020

Cells

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“…Aberration of SHH signaling has been linked with tumorigenesis in various tissues, as for instance found in pancreas (Kasai 2016), bladder (Syed et al 2016) and prostate (Peng & Joyner 2015). Similar to the NOTCH pathway, SHH activity appears to differ according to pituitary adenoma subtype.…”

Section: Dysregulation Of Shh In Pituitary Tumorigenesismentioning

confidence: 99%

Pituitary stem cell regulation: who is pulling the strings?

Cox

Roose

Vennekens

et al. 2017

Journal of Endocrinology

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The pituitary gland plays a pivotal role in the endocrine system, steering fundamental processes of growth, metabolism, reproduction and coping with stress. The adult pituitary contains resident stem cells, which are highly quiescent in homeostatic conditions. However, the cells show marked signs of activation during processes of increased cell remodeling in the gland, including maturation at neonatal age, adaptation to physiological demands, regeneration upon injury and growth of local tumors. Although functions of pituitary stem cells are slowly but gradually uncovered, their regulation largely remains virgin territory. Since postnatal stem cells in general reiterate embryonic developmental pathways, attention is first being given to regulatory networks involved in pituitary embryogenesis. Here, we give an overview of the current knowledge on the NOTCH, WNT, epithelial-mesenchymal transition, SHH and Hippo pathways in the pituitary stem/progenitor cell compartment during various (activation) conditions from embryonic over neonatal to adult age. Most information comes from expression analyses of molecular components belonging to these networks, whereas functional extrapolation is still very limited. From this overview, it emerges that the 'big five' embryonic pathways are indeed reiterated in the stem cells of the 'lazy' homeostatic postnatal pituitary, further magnified en route to activation in more energetic, physiological and pathological remodeling conditions. Increasing the knowledge on the molecular players that pull the regulatory strings of the pituitary stem cells will not only provide further fundamental insight in postnatal pituitary homeostasis and activation, but also clues toward the development of regenerative ideas for improving treatment of pituitary deficiency and tumors.

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“…As previous work demonstrated CAFs can induce stem cell-like characteristics in prostate cancer cells and expression of stem cell markers is known to be related to tumorigenesis (Eppert, et al 2011; Geary, et al 2014; Hu, et al 2015; Liao, et al 2010b; Merlos-Suarez, et al 2011; Syed, et al 2016), we investigated if selective suppression of AR in CAFs affected expression of stem cell markers in human prostate cancer cells.…”

Section: Resultsmentioning

confidence: 99%

Androgen receptor in cancer-associated fibroblasts influences stemness in cancer cells

Liao¹,

Chen²,

Luethy³

et al. 2017

Endocrine-Related Cancer

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Androgen receptor (AR) regulation pathways are essential for supporting the growth and survival of prostate cancer cells. Recently, sub-populations of prostate cancer cells have been identified with stem cell features and are associated with the emergence of treatment-resistant prostate cancer. Here, we explored the function of AR in prostate cancer-associated fibroblasts (CAFs) relative to growth and stem-cell associated characteristics. CAFs were isolated from the murine cPten−/− L prostate cancer model and cultured with human prostate cancer epithelial (hPCa) cells. A murine-specific AR antisense oligonucleotide (ASO) was used to suppress expression of AR in the CAF cells. CAFs express low, but significant levels of AR relative to fibroblasts derived from non-malignant tissue. CAFs promoted growth and colony formation of hPCa cells which was attenuated by suppression of AR expression. Surprisingly, AR-depleted CAFs promoted increased stem cell marker expression in hPCa cells. Interferon gamma (IFN-γ) and macrophage colony stimulating factor (M-CSF) were increased in AR-depleted CAF cells and exhibited similar effects on stem cell marker expression as seen in the CAF co-culture systems. Clinically, elevated IFN-γ expression was found to correlate with histologic grade in primary prostate cancer samples. In summary, AR and androgen-dependent signaling is active in CAFs and exerts significant effects on prostate cancer cells. IFN-γ and M-CSF are AR-regulated factors secreted by CAF cells which promote expression of stem cell markers in prostate cancer epithelial cells. Understanding how CAFs and other constituents of stromal tissue react to anti-cancer therapies may provide insight into the development and progression of prostate cancer.

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Role of Sonic Hedgehog (Shh) Signaling in Bladder Cancer Stemness and Tumorigenesis

Cited by 30 publications

References 57 publications

Emerging Roles of Cancer Stem Cells in Bladder Cancer Progression, Tumorigenesis, and Resistance to Chemotherapy: A Potential Therapeutic Target for Bladder Cancer

Emerging Roles of Cancer Stem Cells in Bladder Cancer Progression, Tumorigenesis, and Resistance to Chemotherapy: A Potential Therapeutic Target for Bladder Cancer

Pituitary stem cell regulation: who is pulling the strings?

Androgen receptor in cancer-associated fibroblasts influences stemness in cancer cells

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