<i>AXIN2</i> Polymorphisms and Their Association with Colorectal Cancer in Mexican Patients

Rosales-Reynoso, Mónica Alejandra; Arredondo-Valdez, Abril Reneé; Wence-Chavez, L I; Barros‐Núñez, Patricio; Gallegos‐Arreola, Martha Patricia; Flores-Martínez, Silvia Esperanza; Sánchez‐Corona, José

doi:10.1089/gtmb.2016.0026

Cited by 18 publications

(19 citation statements)

References 30 publications

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“…Thus, this diminished sensitivity of axin2 for inhibition by upstream signalling provides an elegant explanation for the effective restoration of destruction complex activity by axin2 (Bernkopf et al, ). The importance of axin2‐mediated feedback is further illustrated by the clear association between axin2 germline variants with increased cancer risk (Liu et al, ; Aristizabal‐Pachon et al, ; Rosales‐Reynoso et al, ; Bahl et al, ) and the occurrence of somatic axin2 frameshift mutations in various types of cancer (Mazzoni and Fearon, ; Li et al, ).…”

Section: Axin2/conductin‐mediated Feedback Promotes β‐Catenin Destrucmentioning

confidence: 99%

Molecular regulation and pharmacological targeting of the β‐catenin destruction complex

Kappel

Maurice

2017

British J Pharmacology

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The β‐catenin destruction complex is a dynamic cytosolic multiprotein assembly that provides a key node in Wnt signalling regulation. The core components of the destruction complex comprise the scaffold proteins axin and adenomatous polyposis coli and the Ser/Thr kinases casein kinase 1 and glycogen synthase kinase 3. In unstimulated cells, the destruction complex efficiently drives degradation of the transcriptional coactivator β‐catenin, thereby preventing the activation of the Wnt/β‐catenin pathway. Mutational inactivation of the destruction complex is a major pathway in the pathogenesis of cancer. Here, we review recent insights in the regulation of the β‐catenin destruction complex, including newly identified interaction interfaces, regulatory elements and post‐translationally controlled mechanisms. In addition, we discuss how mutations in core destruction complex components deregulate Wnt signalling via distinct mechanisms and how these findings open up potential therapeutic approaches to restore destruction complex activity in cancer cells.Linked ArticlesThis article is part of a themed section on WNT Signalling: Mechanisms and Therapeutic Opportunities. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.24/issuetoc

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Section: Axin2/conductin‐mediated Feedback Promotes β‐Catenin Destrucmentioning

confidence: 99%

Molecular regulation and pharmacological targeting of the β‐catenin destruction complex

Kappel

Maurice

2017

British J Pharmacology

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“…In addition, four genes (CCND1, WNT2, MET, and HDAC2) of the 11 genes were contained by the five known cancer gene sets (Table S8). Specifically, CyclinD1 (CCND1) polymorphisms were associated with CRC [30]; WNT2, a member of the WNT gene family, is involving in a signaling pathway which can promote colorectal cancer progression [31]; MET (MET Proto-Oncogene) may act as prognosis biomarkers for CRC [32]; HDAC2 (Histone Deacetylase 2) was found to be a potential target in CRC [33]. Besides, literature searches found that our method could also identify new biomarkers not contained by the five know cancer gene sets.…”

Section: Discussionmentioning

confidence: 99%

Network-based identification of biomarkers for colon adenocarcinoma

Wang

Yang

et al. 2020

BMC Cancer

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Background: As one of the most common cancers with high mortality in the world, we are still facing a huge challenge in the prevention and treatment of colon cancer. With the rapid development of high throughput technologies, new biomarkers identification for colon cancer has been confronted with the new opportunities and challenges. Methods: We firstly constructed functional networks for each sample of colon adenocarcinoma (COAD) by using a sample-specific network (SSN) method which can construct individual-specific networks based on gene expression profiles of a single sample. The functional genes and interactions were identified from the functional networks, respectively. Results: Classification and subtyping were used to test the function of the functional genes and interactions. The results of classification showed that the functional genes could be used as diagnostic biomarkers. The subtypes displayed different mechanisms, which were shown by the functional and pathway enrichment analysis for the representative genes of each subtype. Besides, subtype-specific molecular patterns were also detected, such as subtype-specific clinical and mutation features. Finally, 12 functional genes and 13 functional edges could serve as prognosis biomarkers since they were associated with the survival rate of COAD. Conclusions: In conclusion, the functional genes and interactions in the constructed functional network could be used as new biomarkers for COAD.

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“…The Axin2 rs2240308 polymorphism has been widely implicated in cancer risk; however, the results of studies exploring this association were inconclusive. For example, a previous study reported that a rs2240308 variant genotype significantly increased the risk of colorectal cancer in Mexican individuals [4]. In contrast, the same variant exhibited no significant association of colorectal cancer risk among Iranian people and resulted in an effect value that was opposite relative to the study of Mexican populations [5].…”

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confidence: 95%

“…In contrast, the same variant exhibited no significant association of colorectal cancer risk among Iranian people and resulted in an effect value that was opposite relative to the study of Mexican populations [5]. Regardless, an increasing number of studies have given special attention to the association between Axin2 rs2240308 and several common types of cancer such as lung cancer [6][7][8], prostate cancer [9,10], colorectal cancer [4,5,8], ovarian cancer [11], head and neck cancer [8], breast cancer [12], papillary thyroid carcinoma [13], hepatocellular carcinoma [14] and astrocytoma [15]. Moreover, several studies summarized the associations of Axin2 rs2240308 with cancer risk by meta-analyses [16][17][18].…”

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confidence: 99%

New concept of the Axin2 rs2240308 polymorphism and cancer risk: an updated meta-analysis

Yu¹,

Tao²,

Liu³

et al. 2017

neo

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Previous meta-analyses reported that the variant T allele of Axin2 rs2240308 is associated with a decreased cancer risk. However, more recent findings have been inconsistent. Therefore, we carried out an updated meta-analysis to examine whether this polymorphism is still associated with a decreased cancer risk. Twelve articles, including 14 case-control studies (2,215 cases and 2,481 controls), were included in our study. Surprisingly, different from previous meta-analyses, no significant association between Axin2 rs2240308 polymorphism and cancer risk was observed (dominant model: OR=0.85; 95% CI=0.68-1.06). In further stratified analyses, rs2240308 was significantly associated with a decreased cancer risk only in Asians (dominant model: OR=0.76; 95% CI=0.66-0.88), while for Caucasians the variant showed no significant association with cancer risk (dominant model: OR=1.09; 95% CI=0.67-1.76). Moreover, the rs2240308 variant exhibited a significant association with a decreased risk of lung cancer and prostate cancer. These findings provided new evidence that differed from previous meta-analyses; Axin2 rs2240308 may not modify general cancer susceptibility. Similar with previous meta-analyses, our analysis indicated that Axin2 rs2240308 may modify cancer susceptibility in an ethnicity- and/or type-specific manner. These findings indicate that further replication studies with large sample sizes are warranted to re-evaluate the relationship between Axin2 rs2240308 and cancer risk, especially in Caucasians.

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AXIN2 Polymorphisms and Their Association with Colorectal Cancer in Mexican Patients

Abstract: Our results indicate the possibility that variations in the AXIN2 gene may play a significant role in promoting or preventing CRC development.

Cited by 18 publications

References 30 publications

Molecular regulation and pharmacological targeting of the β‐catenin destruction complex

Molecular regulation and pharmacological targeting of the β‐catenin destruction complex

Network-based identification of biomarkers for colon adenocarcinoma

New concept of the Axin2 rs2240308 polymorphism and cancer risk: an updated meta-analysis

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