scholarly journals Dietary Factors in the Control of Gut Homeostasis, Intestinal Stem Cells, and Colorectal Cancer

Nutrients ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 2936 ◽  
Author(s):  
Federica Francescangeli ◽  
Maria Laura De Angelis ◽  
Ann Zeuner
Keyword(s):  
Colorectal Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Low Income ◽  
Dietary Factors ◽  
Intestinal Stem Cells ◽  
Intestinal Homeostasis ◽  
Increased Risk ◽  
Incidence And Mortality

Colorectal cancer (CRC) is the third commonly diagnosed cancer and the second leading cause of cancer-related deaths worldwide. Global CRC burden is expected to increase by 60% in the next decade, with low-income countries experiencing an escalation of CRC incidence and mortality in parallel to the adoption of western lifestyles. CRC incidence is also sharply increasing in individuals younger than 50 years, often presenting at advanced stages and with aggressive features. Both genetic and environmental factors have been recognized as major contributors for the development of CRC, the latter including diet-related conditions such as chronic inflammation and obesity. In particular, a diet rich in fat and sugars (Western-style diet, WSD) has been shown to induce multiple pathophysiological changes in the intestine linked to an increased risk of CRC. In this scenario, dietary factors have been recently shown to play novel unexpected roles in the regulation of intestinal stem cells (ISCs) and of the gut microbiota, which represent the two main biological systems responsible for intestinal homeostasis. Furthermore, diet is increasingly recognized to play a key role in the neoplastic transformation of ISCs and in the metabolic regulation of colorectal cancer stem cells. This review illustrates novel discoveries on the role of dietary components in regulating intestinal homeostasis and colorectal tumorigenesis. Particular focus is dedicated to new areas of research with potential clinical relevance including the effect of food components on ISCs and cancer stem cells (CSCs), the existence of CRC-specific microbial signatures and the alterations of intestinal homeostasis potentially involved in early-onset CRC. New insights on the role of dietary factors in intestinal regulation will provide new tools not only for the prevention and early diagnosis of CRC but also for improving the effectiveness of current CRC therapies.

Mo1152 The Role of Cancer Stem Cells in the Increased Risk of Colorectal Cancer in African-Americans

2014 ◽  
Vol 146 (5) ◽  
pp. S-571
Author(s):  
Fadi Antaki ◽  
Lulu Farhana ◽  
Lawrence A. Miller ◽  
Mohammad R. Anees ◽  
Yingjie Yu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Stem Cells ◽  
African Americans ◽  
Cancer Stem Cells ◽  
Increased Risk

Abstract 1083: A novel role of SRC in mediating bypass resistance to MEK inhibition in colorectal cancer stem cells

2021 ◽  
Author(s):  
Mingli Yang ◽  
Thomas B. Davis B. Davis ◽  
Michael V. Nebozhyn ◽  
Andrey Loboda ◽  
Heiman Wang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Mek Inhibition ◽  
Colorectal Cancer Stem Cells

scholarly journals Unveiling role of sphingosine-1-phosphate receptor 2 as a brake of epithelial stem cell proliferation and a tumor suppressor in colorectal cancer

2020 ◽  
Vol 39 (1) ◽  
Author(s):  
Luciana Petti ◽  
Giulia Rizzo ◽  
Federica Rubbino ◽  
Sudharshan Elangovan ◽  
Piergiuseppe Colombo ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Stem Cells ◽  
Cell Proliferation ◽  
Stem Cell ◽  
Tumor Suppressor ◽  
Normal Mucosa ◽  
Intestinal Stem Cells ◽  
Intestinal Epithelial ◽  
Sphingosine 1 Phosphate

Abstract Background Sphingosine-1-phosphate receptor 2 (S1PR2) mediates pleiotropic functions encompassing cell proliferation, survival, and migration, which become collectively de-regulated in cancer. Information on whether S1PR2 participates in colorectal carcinogenesis/cancer is scanty, and we set out to fill the gap. Methods We screened expression changes of S1PR2 in human CRC and matched normal mucosa specimens [N = 76]. We compared CRC arising in inflammation-driven and genetically engineered models in wild-type (S1PR2+/+) and S1PR2 deficient (S1PR2−/−) mice. We reconstituted S1PR2 expression in RKO cells and assessed their growth in xenografts. Functionally, we mimicked the ablation of S1PR2 in normal mucosa by treating S1PR2+/+ organoids with JTE013 and characterized intestinal epithelial stem cells isolated from S1PR2−/−Lgr5-EGFP- mice. Results S1PR2 expression was lost in 33% of CRC; in 55%, it was significantly decreased, only 12% retaining expression comparable to normal mucosa. Both colitis-induced and genetic Apc+/min mouse models of CRC showed a higher incidence in size and number of carcinomas and/or high-grade adenomas, with increased cell proliferation in S1PR2−/− mice compared to S1PR2+/+ controls. Loss of S1PR2 impaired mucosal regeneration, ultimately promoting the expansion of intestinal stem cells. Whereas its overexpression attenuated cell cycle progression, it reduced the phosphorylation of AKT and augmented the levels of PTEN. Conclusions In normal colonic crypts, S1PR2 gains expression along with intestinal epithelial cells differentiation, but not in intestinal stem cells, and contrasts intestinal tumorigenesis by promoting epithelial differentiation, preventing the expansion of stem cells and braking their malignant transformation. Targeting of S1PR2 may be of therapeutic benefit for CRC expressing high Lgr5. Graphical Abstract. Schematic drawing of the role of S1PR2 in normal mucosa and colorectal cancer. In the normal mucosa, S1PR2 is highly expressed by differentiated cells at the upper region of both colon and intestinal crypts (S1PR2 ON), but not by the undifferentiated stem cell at the base of the crypts (S1PR2 OFF), in which acts as a negative proliferative regulator promoting epithelial differentiation. Its loss leads to the expansion of stem cells and reduced levels of PTEN and Axin-2, two negative regulators respectively of PI3K/AKT and Wnt signaling that control β-catenin signaling. The translocation of β-catenin into the nucleus promotes the transcription of target genes involved in the proliferation and malignant transformation. Thereby, S1PR2 works in the intestine as a tumor suppressor

Dietary Choices Modulate Colorectal Cancer Stem Cells: A Role of FXR Nuclear Receptor

2020 ◽  
pp. 1-8
Author(s):  
Nilesh Kumar Sharma ◽  
Sachin C. Sarode ◽  
Gargi S Sarode ◽  
Shankargouda Patil ◽  
Jayanta K. Pal
Keyword(s):  
Colorectal Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Nuclear Receptor ◽  
Dietary Choices ◽  
Colorectal Cancer Stem Cells

scholarly journals Stress responsive miR-31 is a major modulator of mouse intestinal stem cells during regeneration and tumorigenesis

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Yuhua Tian ◽  
Xianghui Ma ◽  
Cong Lv ◽  
Xiaole Sheng ◽  
Xiang Li ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Stem Cells ◽  
Radiation Injury ◽  
Intestinal Stem Cells ◽  
Potential Therapeutic Target ◽  
Intestinal Homeostasis ◽  
Intestinal Tumorigenesis ◽  
Stat3 Signaling ◽  
Coordinate Control ◽  
Stat3 Signaling Pathway

Intestinal regeneration and tumorigenesis are believed to be driven by intestinal stem cells (ISCs). Elucidating mechanisms underlying ISC activation during regeneration and tumorigenesis can help uncover the underlying principles of intestinal homeostasis and disease including colorectal cancer. Here we show that miR-31 drives ISC proliferation, and protects ISCs against apoptosis, both during homeostasis and regeneration in response to ionizing radiation injury. Furthermore, miR-31 has oncogenic properties, promoting intestinal tumorigenesis. Mechanistically, miR-31 acts to balance input from Wnt, BMP, TGFβ signals to coordinate control of intestinal homeostasis, regeneration and tumorigenesis. We further find that miR-31 is regulated by the STAT3 signaling pathway in response to radiation injury. These findings identify miR-31 as a critical modulator of ISC biology, and a potential therapeutic target for a broad range of intestinal regenerative disorders and cancers.

scholarly journals Colorectal Cancer Biomarkers and the Potential Role of Cancer Stem Cells

2013 ◽  
Vol 4 (3) ◽  
pp. 241-250 ◽  
Author(s):  
Russell C. Langan ◽  
John E. Mullinax ◽  
Manish T. Raiji ◽  
Trevor Upham ◽  
Thomas Summers ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Potential Role ◽  
Cancer Biomarkers

scholarly journals The Role of Colorectal Cancer Stem Cells in Metastatic Disease and Therapeutic Response

Cancers ◽  
2011 ◽  
Vol 3 (1) ◽  
pp. 319-339 ◽  
Author(s):  
Eric C. Anderson ◽  
Crystal Hessman ◽  
Trevor G. Levin ◽  
Marcus M. Monroe ◽  
Melissa H. Wong
Keyword(s):  
Colorectal Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Metastatic Disease ◽  
Therapeutic Response ◽  
Colorectal Cancer Stem Cells

scholarly journals FTO-mediated cytoplasmic m6Am demethylation adjusts stem-like properties in colorectal cancer cell

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Sébastien Relier ◽  
Julie Ripoll ◽  
Hélène Guillorit ◽  
Amandine Amalric ◽  
Cyrinne Achour ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Messenger Rna ◽  
Cancer Biology ◽  
Biological Function ◽  
Cancer Management ◽  
Demethylase Activity

AbstractCancer stem cells (CSCs) are a small but critical cell population for cancer biology since they display inherent resistance to standard therapies and give rise to metastases. Despite accruing evidence establishing a link between deregulation of epitranscriptome-related players and tumorigenic process, the role of messenger RNA (mRNA) modifications in the regulation of CSC properties remains poorly understood. Here, we show that the cytoplasmic pool of fat mass and obesity-associated protein (FTO) impedes CSC abilities in colorectal cancer through its N6,2’-O-dimethyladenosine (m6Am) demethylase activity. While m6Am is strategically located next to the m7G-mRNA cap, its biological function is not well understood and has not been addressed in cancer. Low FTO expression in patient-derived cell lines elevates m6Am level in mRNA which results in enhanced in vivo tumorigenicity and chemoresistance. Inhibition of the nuclear m6Am methyltransferase, PCIF1/CAPAM, fully reverses this phenotype, stressing the role of m6Am modification in stem-like properties acquisition. FTO-mediated regulation of m6Am marking constitutes a reversible pathway controlling CSC abilities. Altogether, our findings bring to light the first biological function of the m6Am modification and its potential adverse consequences for colorectal cancer management.

scholarly journals Role of cancer stem cells in racial disparity in colorectal cancer

2016 ◽  
Vol 5 (6) ◽  
pp. 1268-1278 ◽  
Author(s):  
Lulu Farhana ◽  
Fadi Antaki ◽  
Mohammad R. Anees ◽  
Pratima Nangia‐Makker ◽  
Stephanie Judd ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Racial Disparity
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