Residual tumor cells after chemotherapy in colorectal cancer are LGR5-positive cancer stem cells and their ability to eliminate reactive oxygen species is elevated.
We found that LGR5 expression in the epithelium and stroma was associated with tumor stage, and by integrating functional experiments with LGR5-sorted cell RNA sequencing data from adenoma and normal organoids, we found correlations between LGR5 and CRC-specific genes, including dickkopf WNT signaling pathway inhibitor 4 (<i>DKK4</i>) and SPARC-related modular calcium binding 2 (<i>SMOC2</i>).
Most importantly, Lgr5+CD44+EpCAM+ cells exhibited more pronounced CSC-like traits than did any other subpopulation, indicating that Lgr5 combined with CD44 and EpCAM can further improve the stem-like traits of CSCs in colorectal cancer.
The results of the present study suggest that the nuclear expression of β-catenin and LGR5 and the cytoplasmic expression of GATA6 function together during the development of colorectal carcinoma.
LGR5 has an important role in the EGF-mediated survival and proliferation of early adenoma cells and could have clinical utility in predicting response of CRC patients to EGFR therapy.
Tumor necrosis factor receptor superfamily member 19 (<i>TROY</i>) is involved in the Wnt/β-catenin signaling pathway and interacts with leucine-rich repeat containing G-protein-coupled receptor 5 (LGR5), which is a well-known biomarker of cancer stem cells and a prognostic marker of colorectal cancer (CRC).
This expansion of the LGR5 compartment coincides with maintenance of crypt-like glandular structure (adenomas, and well and moderately differentiated adenocarcinomas), and is reduced in poorly differentiated CRC, where crypt-like glandular architecture is lost, accompanied by reduced epithelial terminal differentiation.
We found that HOXA4 and HOXA9 are up-regulated in CRC SCs. siRNA knockdown of HOXA4 and HOXA9 reduced: (i) proliferation and sphere-formation and (ii) gene expression of known SC markers (ALDH1, CD166, LGR5).
It will further highlight recent studies indicating the plasticity or redundancy of LGR5<sup>+</sup> cells in intestinal cancer progression and assess the overall merit of therapeutically targeting LGR5 in CRC.
Here we show that the leucine-rich repeat-containing G-protein-coupled receptor 5 (Lgr5) identifies intestinal CSCs in mouse tumours engineered to recapitulate the clinical progression of human colorectal cancer.
Overall, our results define a critical function for miR-23b, which, by targeting LGR5, contributes to overpopulation of ALDH<sup>+</sup> CSCs and colorectal cancer.<i></i>.
Counting results showed that the grading scores of cells positive for LGR5 and ALDH1 in the adenoma/CRC epithelium were significantly increased relative with the control epithelium, and associated with the degree of dysplasia in the adenoma and node involvement in the CRC (all P < 0.05).
Obesity is a major risk factor for colorectal cancer and can accelerate Lgr5+ intestinal stem cell (ISC)-derived tumorigenesis after the inactivation of <i>Apc</i> However, whether non-canonical pathways involving PI3K-Akt signaling in ISCs can lead to tumor formation, and if this can be further exacerbated by obesity is unknown.