Tumor-Associated Macrophages Derived TGF-β‒Induced Epithelial to Mesenchymal Transition in Colorectal Cancer Cells through Smad2,3-4/Snail Signaling Pathway

Cai, Jun; Xia, Limin; Li, Jinlei; Ni, Shi-chang; Song, Huayu; Wu, Xuesong

doi:10.4143/crt.2017.613

Cited by 97 publications

(78 citation statements)

References 31 publications

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“…As the pivotal factor of the transforming growth factor β pathway, which regulates tumorigenesis and tumor progression, SMAD4 mutations were reported to be present in 2.1%-20.0% of CRC [26]. In a meta-analysis, Huang et al [18] reported that patients with CRC who had a KRAS mutation (combined odds ratio [OR], 1.29; 95% CI, 1.13 to 1.47) or SMAD4 mutation (combined OR, 2.04; 95% CI, 1.41 to 2.95) were at a higher risk of distant metastasis.…”

Section: Discussionmentioning

confidence: 99%

Clinical Implication of Concordant or Discordant Genomic Profiling between Primary and Matched Metastatic Tissues in Patients with Colorectal Cancer

Choi

Lee

et al. 2020

Cancer Res Treat

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Original ArticlePurpose The purpose of this study was to identify the concordant or discordant genomic profiling between primary and matched metastatic tumors in patients with colorectal cancer (CRC) and to explore the clinical implication. Materials and MethodsSurgical samples of primary and matched metastatic tissues from 158 patients (335 samples) with CRC at Korea University Anam Hospital were evaluated using the Ion AmpliSeq Cancer Hotspot Panel. We compared genetic variants and classified them as concordant, primary-specific, and metastasis-specific variants. We used a combination of principal components analysis and clustering to find genomic groups. Kaplan-Meier curves were used to appraise survival between genomic groups. We used machine learning to confirm the correlation between genetic variants and metastatic sites. ResultsA total of 282 types of deleterious non-synonymous variants were selected for analysis. Of a total of 897 variants, an average of 40% was discordant. Three genomic groups were yielded based on the genomic discrepancy patterns. Overall survival differed significantly between the genomic groups. The poorest group had the highest proportion of concordant KRAS G12V and additional metastasis-specific SMAD4. Correlation analysis between genetic variants and metastatic sites suggested that concordant KRAS mutations would have more disseminated metastases. ConclusionDriver gene mutations were mostly concordant; however, discordant or metastasis-specific mutations were present. Clinically, the concordant driver genetic changes with additional metastasis-specific variants can predict poor prognosis for patients with CRC.

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Section: Discussionmentioning

confidence: 99%

Clinical Implication of Concordant or Discordant Genomic Profiling between Primary and Matched Metastatic Tissues in Patients with Colorectal Cancer

Choi

Lee

et al. 2020

Cancer Res Treat

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“…We also tested epithelial-mesenchymal transition (EMT)associated protein. In consistent with these results, increased CARD9 was accompanied with decreased N-cadherin and transforming growth factor-!, which were able to facilitate EMT process [12], though E-cadherin and vimentin were unch-anged (Fig. 3C).…”

Section: Table 3 Correlation Between Card9 Expression and The Clinicmentioning

confidence: 99%

“…In our opinion, for one thing, the expression of CARD9 varied in different NSCLC cells, a suggestion of important role of CARD9 within NSCLC cells for tumor development. For another, it is typical of tumor to accumulate myeloid cells [10], such as macrophages [12,20], which should lead to increased CARD9 in vivo. We surmised that dramatical downregulation of CARD9 in NSCLC cells contributed to the decreased CARD9 in vivo, which may play a role in NSCLC development.…”

Section: E C T O R C a R D 9 S H C O N T R O L S H C A R Dmentioning

confidence: 99%

Caspase Recruitment Domain Containing Protein 9 Suppresses Non-Small Cell Lung Cancer Proliferation and Invasion via Inhibiting MAPK/p38 Pathway

et al. 2020

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PurposeCaspase recruitment domain containing protein 9 (CARD9) has been demonstrated to be a pro-tumor factor in various cancers. However, our previous study found a significant decrease of CARD9 in malignant pleural effusion compared with benign pleural effusion. So we investigated the role of CARD9 in non-small cell lung cancer (NSCLC) and its working mechanism. Materials and MethodsImmunohistochemistry, western blot, and quantitative real-time polymerase chain reaction were used to detect the expression of CARD9 in specimens of NSCLC patients. The Cancer Genome Atlas (TCGA) databasewas also used to analyze the expression of CARD9 in NSCLC and its predicting value for prognosis. Immunofluorescence was used for CARD9 cellular location. Cell growth assay, clonal formation assay, wound healing assay, matrigel invasion assay, and flow cytometry were used to test cell proliferation, migration, invasion, apoptosis, and cycle progression of NSCLC cells with CARD9 knockdown or CARD9 overexpression. Co-immunoprecipitation was used to identify the interaction between CARD9 and B-cell lymphoma 10 (BCL10). SB203580 was used to inhibit p38 activation.ResultsCARD9 was decreased in NSCLC tissues compared with normal tissues; low CARD9 expression was associated with poor survival. CARD9 was expressed both in tumor cells and macrophages. Downregulation of CARD9 in NSCLC cells enhanced the abilities of proliferation, invasion and migration via activated MAPK/p38 signaling, while overexpression of CARD9 presented antitumor effects. BCL10 was identified to interact with CARD9.ConclusionWe demonstrate that CARD9 is an independent prognostic factor in NSCLC patients and inhibits proliferation, migration, and invasion by suppressing MAPK/p38 pathway in NSCLC cells.

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“…One of the main features of tumor cells during tumor progression is their enhanced migration, invasiveness, and angiogenesis through the epithelial-mesenchymal transition (EMT) process. Several lines of evidence have indicated that TAMs are capable of promoting EMT of tumor cells through their secreted factors, including growth factors and cytokines, such as the previously mentioned epidermal growth factor (EGF), and transforming growth factor-β (TGF-β) [52][53][54][55]. Co-culture of M2 macrophages that were polarized from THP1 monocytes with oral cancer or head and neck squamous cancer cells induced the EMT of carcinoma cells through the EGFR pathway and its downstream target ERK in cancer cells [52].…”

Section: Activation Of Cell-stimulating Growth Factors and Cytokinesmentioning

confidence: 99%

Signaling of Macrophages that Contours the Tumor Microenvironment for Promoting Cancer Development

Messex

Byrd

Liou

2020

Cells

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The immune response is critical in the maintenance of an organism's health. The immune response can be broken down into two groups. The innate response, which is fast-acting and rids the body of most foreign material before infection occurs, and the adaptive response, a more specific defense against pathogen composed mostly of antibody production and killer cells. Linking the two responses via cytokine and chemokine secretion are macrophages, motile phagocytic cells that ingest and present foreign material playing a role in the innate and adaptive immune response. Although macrophages are necessary for the survival of an organism, studies have also shown macrophages play a more sinister role in the initiation, progression, and metastasis in tumorous cells. In this comprehensive review, we show how macrophages induce such a response through abnormal cellular signaling and creating a cellular microenvironment conducive for tumor growth and metastasis, as well as the future outlook of this field.

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Tumor-Associated Macrophages Derived TGF-β‒Induced Epithelial to Mesenchymal Transition in Colorectal Cancer Cells through Smad2,3-4/Snail Signaling Pathway

Abstract: Our results demonstrated that TAMs contributed the EMT progression through a TGF-β/Smad2,3-4/Snail signaling pathway, and disrupting this pathway with TGF-β receptor inhibitor could suppress metastasis, readjusting our focus to the connection of TAMs and cancer metastasis.

Cited by 97 publications

References 31 publications

Clinical Implication of Concordant or Discordant Genomic Profiling between Primary and Matched Metastatic Tissues in Patients with Colorectal Cancer

Clinical Implication of Concordant or Discordant Genomic Profiling between Primary and Matched Metastatic Tissues in Patients with Colorectal Cancer

Caspase Recruitment Domain Containing Protein 9 Suppresses Non-Small Cell Lung Cancer Proliferation and Invasion via Inhibiting MAPK/p38 Pathway

Signaling of Macrophages that Contours the Tumor Microenvironment for Promoting Cancer Development

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