Clinical Implications of Intestinal Stem Cell Markers in Colorectal Cancer

Espersen, Maiken Lise Marcker; Olsen, John Elmerdahl; Linnemann, Dorte; Høgdall, Estrid; Troelsen, Jesper T.

doi:10.1016/j.clcc.2014.12.004

Cited by 34 publications

(26 citation statements)

References 105 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This inhibitory function is consistent with the finding that GPR182 expression is significantly reduced in human colon adenocarcinoma -a novel finding that expands the growing cadre of negative regulators of proliferation, including LRIG1, that have been shown to be downregulated during colorectal tumorigenesis (20,(46)(47)(48)(49). Conversely, numerous pro-proliferative ISC markers, such as LGR5, BMI1, and SOX9, have all been shown to be upregulated in human colorectal carcinomas (50).…”

Section: Methodssupporting

confidence: 75%

Orphan Gpr182 suppresses ERK-mediated intestinal proliferation during regeneration and adenoma formation

Kechele¹,

Blue²,

Zwarycz³

et al. 2017

Journal of Clinical Investigation

View full text Add to dashboard Cite

Section: Methodssupporting

confidence: 75%

Orphan Gpr182 suppresses ERK-mediated intestinal proliferation during regeneration and adenoma formation

Kechele¹,

Blue²,

Zwarycz³

et al. 2017

Journal of Clinical Investigation

View full text Add to dashboard Cite

“…They possess the strongest tumor-initiating potential of all tumor cells and promote tumor growth and resistance to many current therapies, including chemo and radiotherapy [14]. Several intestinal stem cell markers have been investigated, such as the leucine-rich repeat-containing G-protein-coupled receptor 5 (Lgr5) and the B cell–specific Moloney murine leukemia virus insertion site 1 (Bmi1) [15–17]. These two markers are also present in the normal gut in two functionally different intestinal stem cell populations; Lgr5 is present in mitotically active stem cells that are sensitive to irradiation and Wnt modulation, while Bmi1 is a marker for a reserve population of resistant quiescent injury-inducible stem cells [18].…”

Section: Introductionmentioning

confidence: 99%

Delta-like 4/Notch signaling promotes Apc Min/+ tumor initiation through angiogenic and non-angiogenic related mechanisms

et al. 2017

View full text Add to dashboard Cite

BackgroundDelta like 4 (Dll4)/Notch signaling is a key regulator of tumor angiogenesis. Additionally, the role of Dll4 has been studied on tumor stem cells. However, as these cells are implicated in tumor angiogenesis, it is conceivable that the effect of Dll4 on these cells may be a consequence of its angiogenic function. Our aim was to evaluate the expression and dissect the functions of Dll4 in the Apc Min/+ model of colorectal cancer.MethodsWe evaluated the protein expression pattern of Dll4 and other Notch members in the Apc Min/+ tumors relatively to the normal gut and compared endothelial-specific with ubiquitous Dll4 knockout mice on an Apc Min/+ background.ResultsAll Notch pathway members were present in the normal small and large intestine and in the adenomas of the same regions. Dll4, all Notch receptors and Hes1 expression seemed upregulated in the tumors, with some regional differences. The same members and Hes5, instead of Hes1, presented ectopic expression in the tumor parenchyma. Dll4 expression was most pronounced in the tumor cells but it was also present in the tumor blood vessels and in other stromal cells. Ubiquitous and endothelial-specific Dll4 deletion led to an equivalent reduction of tumor growth because of a similarly marked tumoral angiogenic phenotype promoting non-productive vasculature and consequently hypoxia and apoptosis. The ubiquitous Dll4 inhibition led to a stronger decrease of tumor multiplicity than the endothelial-specific deletion by further reducing tumor proliferation and tumor stem cell density through upregulation of the cyclin-dependent kinase inhibitors 1C and 1B and downregulation of Myc, Cyclin D1 and D2 independently of β-catenin activation. This phenotype was associated to the observed increased epithelial differentiation deviated towards the secretory lineages by Atoh1 and Klf4 upregulation only in the ubiquitous Dll4 mutants.ConclusionsDll4 seems to promote Apc Min/+ tumorigenesis through both angiogenic and non-angiogenic related mechanisms.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-3036-0) contains supplementary material, which is available to authorized users.

show abstract

“…Wild type and many SOX9 mutants regulate tumor proliferation capacity, notably through regulation of the CSC pool. Nevertheless, SOX9 protein level could not be clearly associated with patient prognosis [31].…”

Section: Sox9mentioning

confidence: 99%

“…As BMI1 has a role in maintaining the intestinal CSC phenotype, high BMI1 expression could indicate the presence of a large CSC population in the tumor. Consequently, high proportion of CSCs in a tumor could be an indicator of poor prognosis [31,54,55].…”

Section: Bmi1mentioning

confidence: 99%

Transcriptional Regulation of the Intestinal Cancer Stem Cell Phenotype

Gleizes¹,

Cavaillès²,

Lapierre³

2018

Gene Expression and Regulation in Mammalian Cells - Transcription Toward the Establishment of Novel Therapeutics

View full text Add to dashboard Cite

Colorectal cancer (CRC) is one of the most frequent cancers worldwide. Current treatments include surgery and chemotherapy, but disease recurrence occurs frequently. The continuous renewal of intestinal epithelium relies on the presence of intestinal stem cells that are also at the origin of CRC and contribute to therapy resistance and metastatic dissemination. Several nuclear signaling pathways and transcription factors regulate both intestinal cell homeostasis and tumorigenesis. However, the transcriptional events that govern the emergence of aggressive therapy-resistant cancer stem cells are still poorly defined. This review summarizes the relevance of transcription factors in intestinal stem cell biology and their involvement in colon cancer development and drug resistance.

show abstract

Clinical Implications of Intestinal Stem Cell Markers in Colorectal Cancer

Cited by 34 publications

References 105 publications

Orphan Gpr182 suppresses ERK-mediated intestinal proliferation during regeneration and adenoma formation

Orphan Gpr182 suppresses ERK-mediated intestinal proliferation during regeneration and adenoma formation

Delta-like 4/Notch signaling promotes Apc Min/+ tumor initiation through angiogenic and non-angiogenic related mechanisms

Transcriptional Regulation of the Intestinal Cancer Stem Cell Phenotype

Contact Info

Product

Resources

About