Role of Stem Cells in Colorectal Cancer Progression and Prognostic and Predictive Characteristics of Stem Cell Markers in Colorectal Cancer

The stromal vascular cell fraction (SVF) of visceral and subcutaneous adipose tissue (VAT and SAT) has increasingly come into focus in stem cell research, since these compartments represent a rich source of multipotent adipose-derived stem cells (ASCs). ASCs exhibit a self- renewal potential and differentiation capacity. Our aim was to study the different expression of embryonic stem cell markers NANOG, SOX2 and OCT3/4 and to evaluate if there exists a hierarchal role in this network in ASCs derived from both SAT and VAT. ASCs were isolated from SAT and VAT biopsies of 72 consenting patients (23 men, 47 women; age 45 ± 10; BMI between 25 and 30 range) undergoing elective open-abdominal surgery. Sphere-forming capability was evaluated by plating cells in low adhesion plastic. Stem cell markers CD90 and CD105 were analyzed by flow cytometry and stem cell transcription factors NANOG, SOX2 and OCT3/4 were detected by immunoblotting and Real-Time PCR. NANOG, SOX2 and OCT3/4 interplay was explored by gene silencing. ASCs from VAT and SAT confirmed their mesenchymal stem cell (MSC) phenotype expressing the specific MSC markers CD90 and CD105 and NANOG, SOX2 and OCT3/4. NANOG silencing induced a significant OCT 3/4 (70% ± 0.05) and SOX2 (75% ± 0.03) down-regulation whereas SOX2 silencing did not affect NANOG gene expression. Adipose tissue is an important source of MSC, and siRNA experiments endorse a hierarchical role of NANOG in the complex transcription network that regulates pluripotency and plasticity.

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Patient-Derived Colorectal Cancer Organoids Upregulate Revival Stem Cell Marker Genes following Chemotherapeutic Treatment

Journal of Clinical Medicine ◽

10.3390/jcm9010128 ◽

2020 ◽

Vol 9 (1) ◽

pp. 128 ◽

Cited By ~ 8

Author(s):

Engel ◽

Chan ◽

Nickless ◽

Hlavca ◽

Richards ◽

...

Keyword(s):

Colorectal Cancer ◽

Stem Cells ◽

Drug Resistance ◽

Stem Cell ◽

Cell Population ◽

Stem Cell Marker ◽

Stem Cell Population ◽

Marker Genes ◽

Stem Cell Markers ◽

Cell Markers

Colorectal cancer stem cells have been proposed to drive disease progression, tumour recurrence and chemoresistance. However, studies ablating leucine rich repeat containing G protein-coupled receptor 5 (LGR5)-positive stem cells have shown that they are rapidly replenished in primary tumours. Following injury in normal tissue, LGR5+ stem cells are replaced by a newly defined, transient population of revival stem cells. We investigated whether markers of the revival stem cell population are present in colorectal tumours and how this signature relates to chemoresistance. We examined the expression of different stem cell markers in a cohort of patient-derived colorectal cancer organoids and correlated expression with sensitivity to 5-fluorouracil (5-FU) treatment. Our findings revealed that there was inter-tumour variability in the expression of stem cell markers. Clusterin (CLU), a marker of the revival stem cell population, was significantly enriched following 5-FU treatment and expression correlated with the level of drug resistance. Patient outcome data revealed that CLU expression is associated with both lower patient survival and an increase in disease recurrence. This suggests that CLU is a marker of drug resistance and may identify cells that drive colorectal cancer progression.

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NANOG Plays a Hierarchical Role in the Transcription Network Regulating the Pluripotency and Plasticity of Adipose Tissue-Derived Stem Cells (ASCs)

10.20944/preprints201701.0088.v2 ◽

2017 ◽

Author(s):

Maria Pitrone ◽

Giuseppe Pizzolanti ◽

Laura Tomasello ◽

Antonina Coppola ◽

Lorenzo Morini ◽

...

Keyword(s):

Stem Cells ◽

Adipose Tissue ◽

Stem Cell ◽

Embryonic Stem ◽

Stem Cell Markers ◽

Transcription Network ◽

Cell Markers ◽

Nanog Gene ◽

Subcutaneous Adipose

The stromal vascular cell fraction (SVF) of visceral and subcutaneous adipose tissue (VAT and SAT) has increasingly come into focus in stem cell research, since these compartments represent a rich source of multipotent adipose-derived stem cells (ASCs). ASCs exhibit a self- renewal potential and differentiation capacity. Our aim was to study the different expression of embryonic stem cell markers NANOG, SOX2 and OCT3/4 and to evaluate if there exists a hierarchal role in this network in ASCs derived from both SAT and VAT. ASCs were isolated from SAT and VAT biopsies of 72 consenting patients (23 men, 47 women; age 45 ± 10; BMI between 25 and 30 range) undergoing elective open-abdominal surgery. Sphere-forming capability was evaluated by plating cells in low adhesion plastic. Stem cell markers CD90 and CD105 were analyzed by flow cytometry and stem cell transcription factors NANOG, SOX2 and OCT3/4 were detected by immunoblotting and Real-Time PCR. NANOG, SOX2 and OCT3/4 interplay was explored by gene silencing. ASCs from VAT and SAT confirmed their mesenchymal stem cell (MSC) phenotype expressing the specific MSC markers CD90, CD105, NANOG, SOX2 and OCT3/4. NANOG silencing induced a significant OCT 3/4 (70% ± 0.05) and SOX2 (75% ± 0.03) down-regulation whereas SOX2 silencing did not affect NANOG gene expression. Adipose tissue is an important source of MSC, and siRNA experiments endorse a hierarchical role of NANOG in the complex transcription network that regulates pluripotency and plasticity.

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Oncogenic Role of Cancer Stem Cell LGR5 in Colorectal Cancer Progression

Canadian Journal of Medicine ◽

10.33844/cjm.2021.60609 ◽

2021 ◽

Vol 3 (4) ◽

pp. 182-190

Author(s):

Sourena Ghorbani Kalkhajeh ◽

Alireza Parsanezhad ◽

Mahdieh Banoei ◽

Maryam Vahidi ◽

Maziar Malekzadeh Kebria ◽

...

Keyword(s):

Colorectal Cancer ◽

Stem Cell ◽

Cancer Stem Cell ◽

Cancer Progression ◽

Colorectal Cancer Progression

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Faculty Opinions recommendation of ILK Expression in Colorectal Cancer Is Associated with EMT, Cancer Stem Cell Markers and Chemoresistance.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.733254991.793550602 ◽

2018 ◽

Author(s):

Avri Ben-Ze'ev

Keyword(s):

Colorectal Cancer ◽

Stem Cell ◽

Cancer Stem Cell ◽

Stem Cell Markers ◽

Cell Markers ◽

Cancer Stem Cell Markers

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PCGF1 promotes epigenetic activation of stemness markers and colorectal cancer stem cell enrichment

Cell Death and Disease ◽

10.1038/s41419-021-03914-2 ◽

2021 ◽

Vol 12 (7) ◽

Author(s):

Guangyu Ji ◽

Wenjuan Zhou ◽

Jingyi Du ◽

Juan Zhou ◽

Dong Wu ◽

...

Keyword(s):

Colorectal Cancer ◽

Stem Cell ◽

Cancer Progression ◽

Molecular Mechanisms ◽

Tumour Progression ◽

Stem Cell Markers ◽

Epigenetic Regulator ◽

Cell Enrichment ◽

Histone Trimethylation

AbstractColorectal cancer (CRC) stem cells are resistant to cancer therapy and are therefore responsible for tumour progression after conventional therapy fails. However, the molecular mechanisms underlying the maintenance of stemness are poorly understood. In this study, we identified PCGF1 as a crucial epigenetic regulator that sustains the stem cell-like phenotype of CRC. PCGF1 expression was increased in CRC and was significantly correlated with cancer progression and poor prognosis in CRC patients. PCGF1 knockdown inhibited CRC stem cell proliferation and CRC stem cell enrichment. Importantly, PCGF1 silencing impaired tumour growth in vivo. Mechanistically, PCGF1 bound to the promoters of CRC stem cell markers and activated their transcription by increasing the H3K4 histone trimethylation (H3K4me3) marks and decreasing the H3K27 histone trimethylation (H3K27me3) marks on their promoters by increasing expression of the H3K4me3 methyltransferase KMT2A and the H3K27me3 demethylase KDM6A. Our findings suggest that PCGF1 is a potential therapeutic target for CRC treatment.

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