Wnt/β-catenin signaling in colorectal cancer: Is therapeutic targeting even possible?

Disoma, Cyrollah; Zhou, Youyou; Li, Shanni; Peng, Jian; Xia, Zanxian

doi:10.1016/j.biochi.2022.01.009

Cited by 37 publications

(18 citation statements)

References 170 publications

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“…1A). As Wnt signaling plays important roles in the progression of CRC [19][20][21][22], we tested whether the expression of downstream target genes of Wnt pathway was affected in these cancer tissues. Similarly, the qRT-PCR results showed that the mRNA expression of Wnt pathway targeting genes, Axin2, c-Myc and Cyclin D1 was also upregulated in CRC tissues (Fig.…”

Section: Uxt-v1 Is Upregulated In Crc Tissuesmentioning

confidence: 99%

UXT-V1 contributes to the malignant phenotypes of colorectal cancer via GSK3β by activating Wnt/β-catenin pathway

Chen

Xiao

et al. 2023

Preprint

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Background: Colorectal cancer (CRC) is one of malignant tumors that seriously threatening human health. β-catenin is a central hub in Wnt pathway, aberrant activation of Wnt/β-catenin signaling pathway promotes the tumorigenesis/progression of CRC. Methods and Results: Here we found a β-catenin interactor, UXT-V1, could modulate Wnt signaling. The expression of UXT-V1 mRNA was increased in CRC tissues. Overexpression of UXT-V1 increased the canonical Wnt signaling, as evidenced by Wnt reporter systems and the up-regulation of marker genes including Axin, CyclinD1 and c-Myc. While, knockdown of UXT-V1 impaired the expression of these genes and attenuated Wnt signaling. Mechanistically, overexpression of UXT-V1 could inhibit GSK3β mediated β-catenin phosphorylation and degradation. Knockout of UXT-V1 increased β-catenin phosphorylation, prevented CRC cell growth, and inhibited tumorigenesis in NOD-SCID mice. Conclusions: Taken together, our findings revealed that UXT-V1 could control Wnt signaling through targeting GSK3β mediated β-catenin phosphorylation and degradation, providing a molecular basis for CRC treatment.

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Section: Uxt-v1 Is Upregulated In Crc Tissuesmentioning

confidence: 99%

UXT-V1 contributes to the malignant phenotypes of colorectal cancer via GSK3β by activating Wnt/β-catenin pathway

Chen

Xiao

et al. 2023

Preprint

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“…CRC remains a life-threatening malignancy, even though there are great improvements in therapies. Approximately 6–10% of CRC patients are caused by genetic mutations, including TP53 and WNT/β-catenin signaling [ 39 ]. For these patients, targeted therapies are developed and some of the patients benefit from the small molecules targeting WNT/β-catenin signaling [ 40 ].…”

Section: Discussionmentioning

confidence: 99%

Matrine impedes colorectal cancer proliferation and migration by downregulating endoplasmic reticulum lipid raft associated protein 1 expression

et al. 2022

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Matrine exhibits anti-tumor effect on the proliferation and invasion of colorectal cancer (CRC) cells by reducing the activity of the p38 signaling pathway. However, these studies were limited because the underlying mechanism by which matrine inhibited CRC progression remained unclear. In this study, we provided for the first time that endoplasmic reticulum lipid raft associated protein 1 (Erlin1) is a novel target of matrine. Erlin1 was significantly upregulated in tumors and its knockdown suppressed the proliferation and migration of CRC cells, while its overexpression promoted CRC cell growth and migration. Furthermore, Erlin1 overexpression promoted inhibited apoptosis. Importantly, matrine treatment could reverse the oncogenic function of Erlin1 on CRC cell proliferation and migration. When Erlin1 was knocked down, matrine exhibited a more obvious anti-tumor effect in CRC cells. Partly due to this, matrine functions as an important anti-tumor drug and the results discovered here may clarify the mechanisms of matrine application for CRC treatment. CRC patients with low expression of Erlin1 might be more suitable for the treatment of matrine. This study could promote the application of matrine to be a promising therapeutic strategy for CRC patients.

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“…In the last decade, therapeutic inhibition of the β-catenin pathway has been considered an invaluable tool for developing new therapy regimens for patients with CRC[ 115 - 117 ]. Despite this, as previously stated, there are still no approved drugs for the treatment of CRC or clinical trials based on the targeting of this signaling pathway[ 15 , 117 ]. For these reasons, comprehension of the regulatory mechanisms of the Wnt/β-catenin signaling pathway will not only expand the knowledge about the pathogenesis and evolution of CRC but also improve the treatment with the implementation of new targeted therapies.…”

Section: The Tme and β-Catenin Pathway: Future Perspectives For Crc M...mentioning

confidence: 99%

“…Furthermore, this pathway became an unquestionable target for novel therapies for CRC. Despite this, to date, there are no approved treatments or clinical trials for CRC based on targeting the Wnt/β-catenin pathway[ 15 ].…”

Section: Introductionmentioning

confidence: 99%

Tumor microenvironment involvement in colorectal cancer progression via Wnt/β-catenin pathway: Providing understanding of the complex mechanisms of chemoresistance

Díaz¹,

Martín²,

Gentili³

2022

WJG

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Colorectal cancer (CRC) continues to be one of the main causes of death from cancer because patients progress unfavorably due to resistance to current therapies. Dysregulation of the Wnt/β-catenin pathway plays a fundamental role in the genesis and progression of several types of cancer, including CRC. In many subtypes of CRC, hyperactivation of the β-catenin pathway is associated with mutations of the adenomatous polyposis coli gene. However, it can also be associated with other causes. In recent years, studies of the tumor microenvironment (TME) have demonstrated its importance in the development and progression of CRC. In this tumor nest, several cell types, structures, and biomolecules interact with neoplastic cells to pave the way for the spread of the disease. Cross-communications between tumor cells and the TME are then established primarily through paracrine factors, which trigger the activation of numerous signaling pathways. Crucial advances in the field of oncology have been made in the last decade. This Minireview aims to actualize what is known about the central role of the Wnt/β-catenin pathway in CRC chemoresistance and aggressiveness, focusing on cross-communication between CRC cells and the TME. Through this analysis, our main objective was to increase the understanding of this complex disease considering a more global context. Since many treatments for advanced CRC fail due to mechanisms involving chemoresistance, the data here exposed and analyzed are of great interest for the development of novel and effective therapies.

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Wnt/β-catenin signaling in colorectal cancer: Is therapeutic targeting even possible?

Cited by 37 publications

References 170 publications

UXT-V1 contributes to the malignant phenotypes of colorectal cancer via GSK3β by activating Wnt/β-catenin pathway

UXT-V1 contributes to the malignant phenotypes of colorectal cancer via GSK3β by activating Wnt/β-catenin pathway

Matrine impedes colorectal cancer proliferation and migration by downregulating endoplasmic reticulum lipid raft associated protein 1 expression

Tumor microenvironment involvement in colorectal cancer progression via Wnt/β-catenin pathway: Providing understanding of the complex mechanisms of chemoresistance

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