<scp>ASPM</scp> facilitates colorectal cancer cells migration and invasion by enhancing β‐catenin expression and nuclear translocation

Wang, Lu; Hu, Xiaodan; Li, Shouying; Liang, Xuyang; Ren, Lin; Lv, Shengxiang

doi:10.1002/kjm2.12464

Cited by 8 publications

(4 citation statements)

References 19 publications

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“…ASPM has been identified as a biomarker for CRC and is upregulated in CRC tissues, functioning to promote proliferation and inhibit apoptosis, affecting the cell cycle ( 69 ). ASPM levels are positively correlated with β-catenin levels ( 70 ). CDK9 , Cyclin-dependent kinase 9 plays a role in transcriptional elongation and has been shown to be a potential drug target in CRC ( 71 ).…”

Section: Resultsmentioning

confidence: 99%

Exhaustive identification of genome-wide binding events of transcriptional regulators

Nordin,

Pagella,

Zambanini

et al. 2024

Nucleic Acids Research

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Genome-wide binding assays aspire to map the complete binding pattern of gene regulators. Common practice relies on replication—duplicates or triplicates—and high stringency statistics to favor false negatives over false positives. Here we show that duplicates and triplicates of CUT&RUN are not sufficient to discover the entire activity of transcriptional regulators. We introduce ICEBERG (Increased Capture of Enrichment By Exhaustive Replicate aGgregation), a pipeline that harnesses large numbers of CUT&RUN replicates to discover the full set of binding events and chart the line between false positives and false negatives. We employed ICEBERG to map the full set of H3K4me3-marked regions, the targets of the co-factor β-catenin, and those of the transcription factor TBX3, in human colorectal cancer cells. The ICEBERG datasets allow benchmarking of individual replicates, comparing the performance of peak calling and replication approaches, and expose the arbitrary nature of strategies to identify reproducible peaks. Instead of a static view of genomic targets, ICEBERG establishes a spectrum of detection probabilities across the genome for a given factor, underlying the intrinsic dynamicity of its mechanism of action, and permitting to distinguish frequent from rare regulation events. Finally, ICEBERG discovered instances, undetectable with other approaches, that underlie novel mechanisms of colorectal cancer progression.

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Section: Resultsmentioning

confidence: 99%

Exhaustive identification of genome-wide binding events of transcriptional regulators

Nordin,

Pagella,

Zambanini

et al. 2024

Nucleic Acids Research

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“…CCNB1 is associated with survival in stage II CRC [26] . Overexpression of cell division cycle protein 20 (CDC20) predicts poor prognosis in CRC patients [27] . Among the remaining hub genes, the mitotic checkpoint gene BUB1 may be a speci c driver of tumor metastasis and progression [28] .…”

Section: Discussionmentioning

confidence: 99%

Bioinformatics analysis reveals link between alternative complement cascade pathway and colorectal cancer liver metastasis

Shi,

Li,

Wei

et al. 2023

Preprint

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Background Colorectal cancer (CRC) has a high incidence mortality rate and is characterized by liver metastasis, which is the main cause of CRC patient death. In this study, a transcriptome sequencing dataset (GSE81558) from the integrated Gene Expression Omnibus database was evaluated to gain new insights into the pathogenesis of CRC and potential therapeutic targets. Methods All raw data were processed using R and screened for differentially expressed genes (DEGs) using LIMMA software. In-depth Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were conducted and visualized using R and Cytoscape software. Protein‒protein interactions (PPIs) associated with the DEGs were assessed using the Search Tool for the Retrieval of Interacting Genes/Proteins database. A mouse model of CRC liver metastasis of CRC was used to verify key associated signaling pathways. Results The GO biological processes (BPs) and KEGG pathway analyses revealed that DEGs between the normal colon and CRC samples were mainly involved in the cell cycle and the P53 signaling pathway, which regulate the cell cycle and alter tumor signaling pathways. The 10 hub genes identified by PPI were cell cycle-related. In CRC versus and CRC liver metastasis samples, the GO BPs were mainly associated with platelets and coagulation, and the KEGG pathways were mainly enriched in the complement and coagulation cascades and drug metabolism. The PPI hub genes were blood protein-related, such as ALB, AHSG, and APOH, or plasma protease inhibitors, such as SERPINC1. To confirm bioinformatics analysis results, we used wild-type (WT), C4 (an important molecule in the classical and lectin complement cascade pathways), and complement factor B (fB, an important molecule in the alternative complement cascade pathway) knockout (KO) mice to construct a CRC liver metastasis model. Compared with WT mice, fB-KO mice demonstrated significantly reduced liver metastasis and inflammation, while there was no difference in C4-KO mice. Conclusion Bioinformatics analyses revealed that the complement cascade is related to CRC liver metastasis and that the cell cycle is related to CRC. The role of the alternative complement pathway in CRC liver metastasis was confirmed in mice, indicating that this pathway is a potential therapeutic target in CRC liver metastasis and providing a theoretical basis for further research.

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“…At present, the main therapeutic strategies for targeting WNT signaling in CRC are focused on inhibiting CTNNB1 expression and protein accumulation, because 75% of CRC patients have APC mutation [2,3]. In fact, the pathological function of WNT signaling is dependent on CTNNB1 nuclear translocation to perform transcriptional regulator, so the relevant mechanism is a hot issue for understanding pathologic WNT signaling in CRC [19][20][21][22]. In this study, we found that LSM12 directly interacts with CTNNB1 to regulate the formation of the CTNNB1-LEF1-TCF1 transcriptional complex.…”

Section: Discussionmentioning

confidence: 99%

LSM12 facilitates the progression of colorectal cancer by activating the WNT/CTNNB1 signaling pathway

ZHUANG¹,

NING²,

Liu³

et al. 2022

Oncology Research

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Aberrant activation of the WNT signaling pathway is a joint event in colorectal cancer (CRC), but the molecular mechanism is still unclear. Recently, RNA-splicing factor LSM12 (like-Sm protein 12) is highly expressed in CRC tissues.This study aimed to verify whether LSM12 is involved in regulating CRC progression via regulating the WNT signaling pathway. Here, we found that LSM12 is highly expressed in CRC patient-derived tissues and cells. LSM12 is involved in the proliferation, invasion, and apoptosis of CRC cells, similar to the function of WNT signaling in CRC. Furthermore, protein interaction simulation and biochemical experiments proved that LSM12 directly binds to CTNNB1 (also known as β-Catenin) and regulates its protein stability to affect the CTTNB1-LEF1-TCF1 transcriptional complex formation and the associated WNT downstream signaling pathway. LSM12 depletion in CRC cells decreased the in vivo tumor growth through repression of cancer cell growth and acceleration of cancer cell apoptosis. Taken together, we suggest that the high expression of LSM12 is a novel factor leading to aberrant WNT signaling activation, and that strategies targeting this molecular mechanism may contribute to developing a new therapeutic method for CRC.

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ASPM facilitates colorectal cancer cells migration and invasion by enhancing β‐catenin expression and nuclear translocation

Cited by 8 publications

References 19 publications

Exhaustive identification of genome-wide binding events of transcriptional regulators

Exhaustive identification of genome-wide binding events of transcriptional regulators

Bioinformatics analysis reveals link between alternative complement cascade pathway and colorectal cancer liver metastasis

LSM12 facilitates the progression of colorectal cancer by activating the WNT/CTNNB1 signaling pathway

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