Dvl2 facilitates the coordination of NF‐κB and Wnt signaling to promote colitis‐associated colorectal progression

Tang, Feiyu; Cao, Fuyang; Lü, Can; He, Xiaoqing; Weng, Liang; Sun, Lun‐Quan

doi:10.1111/cas.15206

Cited by 8 publications

(6 citation statements)

References 36 publications

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“…2) and have possible clinical implications for CRC prevention and therapy. This testing is of particular value given findings of the importance of various signaling pathways in CRC [24][25][26][27][28][29][30], including those that influence Wnt signaling [25,26,[28][29][30]. These other signaling pathways can be included in the categories of (a) receptor-mediated Wnt signaling and/or (b) those related to butyrate resistance [27], and the non-Wnt signaling pathways may exhibit cross-talk with Wnt activity, particularly Wnt activity that is mediated by CBP and p300.…”

Section: Discussionmentioning

confidence: 99%

Oncogenic and Receptor-Mediated Wnt Signaling Influence the Sensitivity of Colonic Cells to Butyrate

Bordonaro¹

2023

J. Cancer

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Deregulated Wnt signaling is responsible for most cases of colorectal cancer (CRC). Dietary fiber is protective against CRC and this activity is likely mediated by butyrate, a breakdown product of dietary fiber that hyperactivates Wnt signaling, repressing CRC proliferation and inducing apoptosis. Receptor-mediated Wnt signaling and oncogenic Wnt signaling, which is typically initiated by mutation in more downstream elements of the pathway, activate non-overlapping patterns of gene expression. Receptor-mediated signaling is associated with a poor prognosis for CRC while oncogenic signaling is associated with a relatively good prognosis. We have compared the expression of genes differentially expressed in receptor-mediated vs. oncogenic Wnt signaling to microarray data generated in our laboratory. Most importantly we evaluated these gene expression patterns comparing the early stage colon microadenoma line LT97 with the metastatic CRC cell line SW620. LT97 cells exhibit a gene expression pattern more strongly associated with that observed with oncogenic Wnt signaling, while SW620 cells exhibit a gene expression pattern moderately associated with that observed with receptor-mediated Wnt signaling. Given that SW620 cells are more advanced and malignant compared to LT97 cells, these findings are generally consistent with the better prognosis observed with tumors exhibiting a more oncogenic Wnt gene expression pattern. Importantly, LT97 cells are more sensitive to the effects of butyrate on proliferation and apoptosis that are CRC cells. We further examine these gene expression patterns in butyrate-resistant vs. butyrate-sensitive CRC cells. Based upon all of these observations, we hypothesize that colonic neoplastic cells exhibiting a more oncogenic as compared to receptor-mediated Wnt signaling gene expression pattern would be more sensitive to the effects of butyrate, and, hence, fiber, than are those cells exhibiting a more receptor-mediated Wnt signaling pattern of expression. Diet-derived butyrate may affect the differential patient outcomes resulting from the two types of Wnt signaling. We further posit that development of butyrate resistance and concomitant changes in Wnt signaling patterns, including associations with CBP and p300, disrupts the association between the two major types of Wnt signaling (receptor-mediated and oncogenic) and neoplastic progression/prognosis. Ideas about testing the hypothesis and therapeutic implications are briefly considered.

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Section: Discussionmentioning

confidence: 99%

Oncogenic and Receptor-Mediated Wnt Signaling Influence the Sensitivity of Colonic Cells to Butyrate

Bordonaro¹

2023

J. Cancer

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“…Due to the essential role NF-κB and Wnt signaling play in CRC, previous studies have reported that elevated NF-κB levels enhance Wnt signaling, with de-differentiation of intestinal epithelial cells and the promotion of tumor initiation. 45 …”

Section: Discussionmentioning

confidence: 99%

Protective Effect of Qingchang Wenzhong Decoction on Colitis and Colitis-Related Carcinogenesis by Regulating Inflammation and Intestinal Fibrosis

Cheng¹,

Li²,

Zhang³

et al. 2023

JIR

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Purpose Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by mucosal inflammation, which may develop into ulcerative colitis-associated carcinogenesis (UCAC) with disease progression. Qingchang Wenzhong Decoction (QCWZD) is a classic and effective prescription for the clinical treatment of UC. QCWZD has been shown to alleviate intestinal mucosal injury in acute and chronic UC models. This study aimed to explore and then verify the pharmacological mechanisms of QCWZD in UC and UCAC therapy. Methods In this study, approaches including microarray analysis, network pharmacology, and biological verification are employed to clarify the mechanism of QCWZD in the treatment of UC and UCAC. TCMSP, Swiss Target Prediction, and Similarity Ensemble Approach were used to investigate the active ingredients and targets of QCWZD. UC and UCAC valid targets were identified by the microarray data in the GEO database (GSE38713 and GSE47908). The core targets were obtained by PPI network and enriched by GO and KEGG. DSS and AOM/DSS mouse models were adopted to verify the above analysis results. Results The enrichment analysis showed that the therapeutic targets of QCWZD enriched in blood circulation, cell adhesion molecules, and pathways of inflammation and cancer such as IL-17 signaling pathway and toll-like receptor signaling pathway were involved in the multiple synergies of QCWZD on UC and UCAC treatment. The results of experiments demonstrated that QCWZD can exert its effects on protecting the intestinal mucosal barrier, regulating inflammation and improving intestinal fibrosis in UC and UCAC and the main mechanism of QCWZD in treatment of UC and UCAC may be related to the activation of the IL-17, NF-κB and TLR4 signaling pathways. Conclusion Our results indicated that QCWZD treated UC and UCAC via multiple targets and pathways and the IL-17, NF-κB and TLR4 signaling pathways may be highly involved in this process.

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“…Mention crosstalk between stemness and immune cells, WNT signaling pathway, must not be overlooked. Tumor-derived WNT would induce a significant release of pro-inflammatory factors, like MPC-1 or IL-6, and attract numbers of immune cells to tumor immune niches helping cancer cells to escape from the immunologic killing, the function of nuclear factor-kB (NF-kB) signal pathway also contained [65][66][67]. Practically speaking, a conserved NF-kB binding site has been found on WNT5A, indicating that the activation of the WNT/b-catenin pathway could stimulate the vital position of NF-kB in both regulations of immune and inflammation [68,69 ].…”

Section: Targeting Crosstalk Between Lung Cancer Stem Cells and Tumor...mentioning

confidence: 99%

Targeting cancer stem cell pathways for lung cancer therapy

Liu

2022

Current Opinion in Oncology

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Purpose of reviewThe unique properties of cancer stem cells (CSCs) make lung cancer untargetable for quite an extended period. The functional mechanism of this cell type has been illustrated step by step. However, the outcomes of lung cancer patients are still lower than expected clinically. The attempts made by scientists to make challenge history against stemness maintenance of lung cancer cells and their druggable targets are worth elucidating. Recent findingsMany agents, including the Bispecific T-cell engager (BiTE) and AMG 119 targeting DLL3-positive cells, are a tremendous breakthrough in the preclinical and clinical treatment of SCLC. More studies focus on targeting CSCs to overcome TKI resistance in NSCLC. The combo targeting of CSC and the immune microenvironment can favor the treatment of lung cancer patients.

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Dvl2 facilitates the coordination of NF‐κB and Wnt signaling to promote colitis‐associated colorectal progression

Cited by 8 publications

References 36 publications

Oncogenic and Receptor-Mediated Wnt Signaling Influence the Sensitivity of Colonic Cells to Butyrate

Oncogenic and Receptor-Mediated Wnt Signaling Influence the Sensitivity of Colonic Cells to Butyrate

Protective Effect of Qingchang Wenzhong Decoction on Colitis and Colitis-Related Carcinogenesis by Regulating Inflammation and Intestinal Fibrosis

Targeting cancer stem cell pathways for lung cancer therapy

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