Verticillin A increases the BIMEL/MCL-1 ratio to overcome ABT-737-resistance in human colon cancer cells by targeting the MEK/ERK pathway

Guan, Yaoyao; Tu, Kai; Huang, Qiqian; Liu, Feiyan

doi:10.1016/j.bbrc.2021.05.103

Cited by 7 publications

(6 citation statements)

References 40 publications

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“…As a digestive tract malignant tumor in the colon, CRC frequently occurs at the junction between rectum and sigmoid colon ( 25 ). CRC occurs in a staged and multi-step way, where the key factors inducing the occurrence and development of CRC are the activation of various oncogenes and the inactivation of tumor suppressor genes ( 26 ).…”

Section: Discussionmentioning

confidence: 99%

SHP-2-induced M2 polarization of tumor associated macrophages via IL-4 regulate colorectal cancer progression

Liu

et al. 2023

Front. Oncol.

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ObjectiveTo explore the effect and molecular mechanism of Src homology region 2 domain-containing protein tyrosine phosphatase-2 (SHP-2) in tumor-associated macrophages (TAMs) repressing the migration and invasion of colorectal cancer (CRC) cells.MethodsThe relevant data sets of human colon specimens were obtained from GEO database, and then the performed correlation analysis, principal component analysis and differentially expressed gene (DEGs) analysis on the samples were conducted. GO and KEGG enrichment analysis were performed on the common DEGs, and then functional interaction prediction was performed to verify the gene regulatory circuit of SHP-2. Furthermore, western blot was used to detect the effect of low expression of SHP-2 on related proteins, including the markers of promoting M2 polarization and exosome secretion, and keys proteins of the PI3K pathway. The relationship between SHP-2 and PI3K pathway was further verified by adding PI3K inhibitor LY294002. Finally, the effect of SHP-2 on the function of colon cancer cells was confirmed by wound healing assay and Transwell assay.ResultsThrough bioinformatics analysis, SHP-2 was screened as a possible key gene affecting CRC. The low expression of SHP-2 promoted the protein levels of Arginase-1 and IL-10 in IL-4 induced M2 macrophages, while inhibited the protein levels of IL-1β and TNF-α. Meanwhile, low expression of SHP-2 was found to similarly promote the expression of p-PI3K, p-AKT, and the release of exosomes. Interestingly, the promotion was suppressed after the addition of the PI3K inhibitor LY294002. In terms of cellular behavior, wound healing and transwell data showed that low expression of SHP-2 enhanced the migration and invasion abilities of CRC cells.ConclusionThe low expression of SHP-2 induced by PHPS1 may regulate M2 polarization of TAMs and release of exosomes through PI3K/AKT pathway, thereby enhancing the migration and invasion ability of CRC cells.

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Section: Discussionmentioning

confidence: 99%

SHP-2-induced M2 polarization of tumor associated macrophages via IL-4 regulate colorectal cancer progression

Liu

et al. 2023

Front. Oncol.

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“…The study on the new drug Enduo showed that the drug had a certain therapeutic effect on colon cancer by blocking the ERK signaling pathway to prevent cell migration [18] . Verticillin A increases the ratio of BIMEL/MCL-1 to overcome ABT-737-resistance in human colon cancer cells by targeting the MEK/ERK pathway [19] . PKCα activated RAS upstream of RAF, MEK and ERK, which induced the arrest of the cell cycle in intestinal cells [20] .…”

Section: Discussionmentioning

confidence: 99%

Seasonal expression of extracellular signal regulated kinases in the colon of wild ground squirrels (Spermophilus dauricus)

et al. 2022

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Background: The aim of this study was to explore the localization and expression of extracellular signal regulated kinase/phospho-extracellular signal regulated kinases (ERK/pERK) in the colonic tissue of wild ground squirrels (Spermophilus dauricus) in the breeding season and the non-breeding season.Methods and Results: Hematoxylin-eosin staining, immunohistochemistry, real-time quantitative PCR and Western blot were used in this study. The histological results showed that the diameter of the colon lumen in the non-breeding season was larger than that in the breeding season, and the number of glandular cells in the non-breeding season was also more than those in the breeding season. The immunochemical results showed that ERK1/2 was expressed in the cytoplasm of goblet cells and intestinal epithelial cells, while pERK1/2 was expressed in the cytoplasm and nucleus of goblet cells and intestinal epithelial cells. The immunolocalization of ERK1/2 and pERK1/2 expression were more obvious in the non-breeding season, especially in intestinal epithelial cells. The results of real-time quantitative PCR and Western blot showed that the expression of ERK1/2 and pERK1/2 in the breeding season was signi cantly lower than that in the non-breeding season.Conclusions: The expression of ERK1/2 and pERK1/2 in the colons of the wild ground squirrels had seasonal changes, which had signi cant increases in the non-breeding season comparing to those in the breeding season. This study revealed the potential role of ERK1/2 in colon to the adaptation of seasonal changes in wild ground squirrel.

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“…Multiple proteins or drugs affected COAD progression via this pathway. For example, Verticillin A could increase the BIM/MCL-1 ratio to overcome ABT-737 resistance in COAD cells by this pathway [ 27 ]. These studies all confirmed that MEK/ERK pathway could serve as a promising target of COAD.…”

Section: Discussionmentioning

confidence: 99%

COPS3 Promotes Proliferation, Invasion, and EMT of Colorectal Cancer Cells by MEK/ERK Pathway

2022

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Colorectal cancer (CRC) is one of the most aggressive cancers with poor prognosis and high mortality. The study of the pathogenesis of CRC is a top priority in providing effective diagnostic and prognostic strategies for CRC. COPS3 protein is a subunit of the COP9 signaling body (CSN), which is closely associated with the development of multiple types of tumors. However, there are few studies on the role of COPS3 in colon adenocarcinoma (COAD). This study investigated the effects of COPS3 on proliferation, motility, and EMT of colorectal cancer cells and related mechanisms. COPS3 was highly expressed in COAD. The depletion of COPS3 suppressed the viability and stimulated the apoptosis of COAD cells. Depletion of COPS3 suppressed the motility and EMT process of COAD cells. Mechanically, we found that COPS3 could mediate MEK/ERK pathway and therefore affected the process of COAD cells. We thought that COPS3 could serve as a promising COAD target.

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Verticillin A increases the BIMEL/MCL-1 ratio to overcome ABT-737-resistance in human colon cancer cells by targeting the MEK/ERK pathway

Cited by 7 publications

References 40 publications

SHP-2-induced M2 polarization of tumor associated macrophages via IL-4 regulate colorectal cancer progression

SHP-2-induced M2 polarization of tumor associated macrophages via IL-4 regulate colorectal cancer progression

Seasonal expression of extracellular signal regulated kinases in the colon of wild ground squirrels (Spermophilus dauricus)

COPS3 Promotes Proliferation, Invasion, and EMT of Colorectal Cancer Cells by MEK/ERK Pathway

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