Interplay between APC and ALDH1B1 in a newly developed mouse model of colorectal cancer

Golla, Jaya Prakash; Kandyliari, Aikaterini; Tan, Wan Ying; Chen, Ying; Orlicky, David J.; Thompson, David C.; Shah, Yatrik M.; Vasiliou, Vasilis

doi:10.1016/j.cbi.2020.109274

Cited by 7 publications

(6 citation statements)

References 35 publications

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“…The current work established MAD2L2's diagnostic and prognostic relevance in COAD, the processes behind its development, and its relationship with immune infiltration and mutation accumulation in hypoxic conditions. In recent years, many genes important for colorectal cancer progression have been identified (Mo et al, 2015;Kundu et al, 2021;Smeby et al, 2020;Golla et al, 2020;Voutsadakis, 2021;Liu et al, 2019aLiu et al, , 2019b, including KRAS, TP53, APC, PIK3CA, PPARD, and MORC2. With the continuous development of high-throughput technology, microarray analysis has been used to identify unknown colorectal cancer-related oncogenes and biological network analysis (Bogaert and Prenen, 2014).…”

Section: Discussionmentioning

confidence: 99%

Increased MAD2L2 expression predicts poor clinical outcome in Colon Adenocarcinoma

Sun¹,

WANG²,

Li³

et al. 2023

Biocell

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Background: Colon adenocarcinoma (COAD) is the second leading cause of cancer death worldwide thus, identification of COAD biomarkers is critical. Mitotic Arrest Deficient 2 Like 2 (MAD2L2) is a key factor in mammalian DNA damage repair and is highly expressed in many malignant tumors. This is a comprehensive study of MAD2L2 expression, its diagnostic value, prognostic analysis, potential biological function, and impact on the immune system of patients with COAD. Methods: Gene expression, clinical relevance, prognostic analysis, diagnostic value, GO/KEGG cluster analysis, data obtained from TCGA, and bioinformatics statistical analysis were performed using the R package. Immune responses to MAD2L2 expression in COAD were analyzed using TIMER. The expression of MAD2L2 in HCT116 cells induced by the inflammatory factor TNF-α was detected using Western blot.Results: Our results underscore the clinical diagnostic value and potential biological significance of MAD2L2 in patients with COAD. A high level of MAD2L2 expression has been found in COAD and correlated with tumor status and colon polyps. ROC curve analysis showed that MAD2L2 expression has high diagnostic value in COAD. Analysis of immune infiltration results showed that MAD2L2 expression was positively correlated with neutrophil levels. The western blot results demonstrated that MAD2L2 was dose-dependently present with TNF-α. GO/KEGG revealed that MAD2L2 overexpressed and coexpressed genes were mostly involved in biological functions, including hypoxia response, response to reduced oxygen levels, mitochondrial translation elongation, and other processes. Conclusion: MAD2L2 as a new COAD biomarker contributes to our understanding of how alterations in gene expression and the immunological environment contribute to the development of colon cancer. Following further investigation, MAD2L2 may prove to be a viable target factor for clinical diagnosis and therapy of COAD.

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Section: Discussionmentioning

confidence: 99%

Increased MAD2L2 expression predicts poor clinical outcome in Colon Adenocarcinoma

Sun¹,

WANG²,

Li³

et al. 2023

Biocell

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“…The most widely utilized GEMM of intestinal cancer is the Apc Min/+ model, which harbors a dominant nonsense mutation in one Apc allele, resulting in the development of multiple intestinal adenomas, primarily in the small intestine, with few occurring in the colorectum. Vasiliou et al crossed Apc flox mice with Cdx2 ERT2 − Cre mice to generate deficient Apc specifically in colon epithelial cells following tamoxifen treatment [ 181 ]. Kevin G et al generated Apc Min/+ ; Kras LSL−G12D/+ ; Villin ERT2−Cre compound mutant mice, carrying a Cre-dependent activated Kras LSL−G12D on the Apc Min/+ background, crossed with mice carrying the Villin ERT2−Cre transgene, which expresses Cre recombinase throughout the intestine, and confirmed an enhancement of tumor development in the colon [ 182 ].…”

Section: Models To Study Pnimentioning

confidence: 99%

Perineural invasion in colorectal cancer: mechanisms of action and clinical relevance

Wang,

Huo,

et al. 2023

Cell Oncol.

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Background In recent years, the significance of the nervous system in the tumor microenvironment has gained increasing attention. The bidirectional communication between nerves and cancer cells plays a critical role in tumor initiation and progression. Perineural invasion (PNI) occurs when tumor cells invade the nerve sheath and/or encircle more than 33% of the nerve circumference. PNI is a common feature in various malignancies and is associated with tumor invasion, metastasis, cancer-related pain, and unfavorable clinical outcomes. The colon and rectum are highly innervated organs, and accumulating studies support PNI as a histopathologic feature of colorectal cancer (CRC). Therefore, it is essential to investigate the role of nerves in CRC and comprehend the mechanisms of PNI to impede tumor progression and improve patient survival. Conclusion This review elucidates the clinical significance of PNI, summarizes the underlying cellular and molecular mechanisms, introduces various experimental models suitable for studying PNI, and discusses the therapeutic potential of targeting this phenomenon. By delving into the intricate interactions between nerves and tumor cells, we hope this review can provide valuable insights for the future development of CRC treatments.

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“…Generating double knockdowns of ALDH1B1 and APC showed that mice with the absence of 1B1 still formed adenoma colorectal tumors; however, the volume was significantly lower compared to the mice with physiological levels of ALDH1B1. Furthermore, the inhibition of ALDH1B1 expression led to the downregulation of both p53 and b-catenin in these models [ 205 ].…”

Section: Current Knowledge On the Association Of Aldh1b1 With Cancer ...mentioning

confidence: 99%

The Concept of Cancer Stem Cells: Elaborating on ALDH1B1 as an Emerging Marker of Cancer Progression

Tsochantaridis

Roupas

Mohlin

et al. 2023

Life

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Cancer is a multifactorial, complex disease exhibiting extraordinary phenotypic plasticity and diversity. One of the greatest challenges in cancer treatment is intratumoral heterogeneity, which obstructs the efficient eradication of the tumor. Tumor heterogeneity is often associated with the presence of cancer stem cells (CSCs), a cancer cell sub-population possessing a panel of stem-like properties, such as a self-renewal ability and multipotency potential. CSCs are associated with enhanced chemoresistance due to the enhanced efflux of chemotherapeutic agents and the existence of powerful antioxidant and DNA damage repair mechanisms. The distinctive characteristics of CSCs make them ideal targets for clinical therapeutic approaches, and the identification of efficient and specific CSCs biomarkers is of utmost importance. Aldehyde dehydrogenases (ALDHs) comprise a wide superfamily of metabolic enzymes that, over the last years, have gained increasing attention due to their association with stem-related features in a wide panel of hematopoietic malignancies and solid cancers. Aldehyde dehydrogenase 1B1 (ALDH1B1) is an isoform that has been characterized as a marker of colon cancer progression, while various studies suggest its importance in additional malignancies. Here, we review the basic concepts related to CSCs and discuss the potential role of ALDH1B1 in cancer development and its contribution to the CSC phenotype.

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Interplay between APC and ALDH1B1 in a newly developed mouse model of colorectal cancer

Cited by 7 publications

References 35 publications

Increased MAD2L2 expression predicts poor clinical outcome in Colon Adenocarcinoma

Increased MAD2L2 expression predicts poor clinical outcome in Colon Adenocarcinoma

Perineural invasion in colorectal cancer: mechanisms of action and clinical relevance

The Concept of Cancer Stem Cells: Elaborating on ALDH1B1 as an Emerging Marker of Cancer Progression

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