Tumor-derived exosomal microRNA-106b-5p activates EMT-cancer cell and M2-subtype TAM interaction to facilitate CRC metastasis

Yang, Chaogang; Dou, Rongzhang; Chen, Wei; Liu, Keshu; Shi, Dongdong; Zhang, Chunxiao; Liu, Qing; Wang, Shuyi; Xiong, Bin

doi:10.1016/j.ymthe.2021.02.006

Cited by 109 publications

(79 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We also found that exosomal miR-106b derived from EMT-CRC cells promoted the M2-like polarisation of macrophages through increasing the level of miR-106b which activating the PI3K γ /AKT/mTOR signalling pathway by directly suppressing programmed cell death 4 (PDCD4) in a post-transcription level (Ref. 12). Izabela et al .…”

Section: Emt-programmed Crc Cells As An Inducer For Tme Educationmentioning

confidence: 89%

“…Our previous studies demonstrated that TAMs could induce EMT of CRC cells via secreting interleukin-6 (IL-6) to activate the JAK2/STAT3/miR-506-3p/FoxQ1 signalling cascade axis (Ref. 7); meanwhile, we also found that EMT-programmed CRC cells could remodel the TME and polarise TAMs to M2 phenotype via release cytokines (such as interleukin-4(IL-4) and interleukin-10(IL-10)) and exosomes, thereby facilitating tumour progression and metastasis (Refs 11, 12). However, in addition to TAMs, there are fibroblasts, T cells, NK cells and neutrophils in TME, which also play an important role in the EMT process of CRC cells.…”

Section: Introductionmentioning

confidence: 92%

“…81). Previously, our group reported the interactions between TAMs and tumour cells for promoting metastasis in CRC in several articles (Refs 7, 8, 9, 11, 12). In clinical specimen, TAMs, identified by CD163 + (a M2-like macrophages markers), are mainly detected at the tumour invasive front and stroma and the presence of CD163 + TAMs at tumour invasive front is associated with the EMT programme in CRC patients (Ref.…”

Section: Tme As a Driver For Emt Programme Of Crc Cellsmentioning

confidence: 99%

“…Our group previously indicated that exosomes derived from CRC cells have a significant role in intercellular communication for inducing M2 macrophage polarisation (Ref. 12). Zhang et al .…”

Section: Tme As a Driver For Emt Programme Of Crc Cellsmentioning

confidence: 99%

See 3 more Smart Citations

Tumour microenvironment: a non-negligible driver for epithelial−mesenchymal transition in colorectal cancer

Han

Wang

Chen

et al. 2021

Expert Rev. Mol. Med.

Self Cite

View full text Add to dashboard Cite

Cancer remains the leading cause of death worldwide, and metastasis is still the major cause of treatment failure for cancer patients. Epithelial–mesenchymal transition (EMT) has been shown to play a critical role in the metastasis cascade of epithelium-derived carcinoma. Tumour microenvironment (TME) refers to the local tissue environment in which tumour cells produce and live, including not only tumour cells themselves, but also fibroblasts, immune and inflammatory cells, glial cells and other cells around them, as well as intercellular stroma, micro vessels and infiltrated biomolecules from the nearby areas, which has been proved to widely participate in the occurrence and progress of cancer. Emerging and accumulating studies indicate that, on one hand, mesenchymal cells in TME can establish ‘crosstalk’ with tumour cells to regulate their EMT programme; on the other, EMT-tumour cells can create a favourable environment for their own growth via educating stromal cells. Recently, our group has conducted a series of studies on the interaction between tumour-associated macrophages (TAMs) and colorectal cancer (CRC) cells in TME, confirming that the interaction between TAMs and CRC cells mediated by cytokines or exosomes can jointly promote the metastasis of CRC by regulating the EMT process of tumour cells and the M2-type polarisation process of TAMs. Herein, we present an overview to describe the current knowledge about EMT in cancer, summarise the important role of TME in EMT, and provide an update on the mechanisms of TME-induced EMT in CRC, aiming to provide new ideas for understanding and resisting tumour metastasis.

show abstract

Section: Emt-programmed Crc Cells As An Inducer For Tme Educationmentioning

confidence: 89%

Section: Introductionmentioning

confidence: 92%

Section: Tme As a Driver For Emt Programme Of Crc Cellsmentioning

confidence: 99%

“…Our group previously indicated that exosomes derived from CRC cells have a significant role in intercellular communication for inducing M2 macrophage polarisation (Ref. 12). Zhang et al .…”

Section: Tme As a Driver For Emt Programme Of Crc Cellsmentioning

confidence: 99%

See 2 more Smart Citations

Tumour microenvironment: a non-negligible driver for epithelial−mesenchymal transition in colorectal cancer

Han

Wang

Chen

et al. 2021

Expert Rev. Mol. Med.

Self Cite

View full text Add to dashboard Cite

show abstract

“…The tumor-derived exocrine miR-934 can promote CRC liver metastasis by regulating the interaction between CRC cells and TAMs (110). In addition, exosomes carrying miRNA-106b-5p promote the M2-like polarization of macrophages and induce the EMT in CRC cells, which is implicated in the crosstalk between tumor cells and TAMs (131). Brahma-related gene-1 (BRG1) is the core subunit of switch/sucrose nonfermentable (SWI/SNF) family complexes (132).…”

Section: Non-coding Rnamentioning

confidence: 99%

Macrophages, as a Promising Strategy to Targeted Treatment for Colorectal Cancer Metastasis in Tumor Immune Microenvironment

Zhang

Zhao

et al. 2021

Front. Immunol.

View full text Add to dashboard Cite

The tumor immune microenvironment plays a vital role in the metastasis of colorectal cancer. As one of the most important immune cells, macrophages act as phagocytes, patrol the surroundings of tissues, and remove invading pathogens and cell debris to maintain tissue homeostasis. Significantly, macrophages have a characteristic of high plasticity and can be classified into different subtypes according to the different functions, which can undergo reciprocal phenotypic switching induced by different types of molecules and signaling pathways. Macrophages regulate the development and metastatic potential of colorectal cancer by changing the tumor immune microenvironment. In tumor tissues, the tumor-associated macrophages usually play a tumor-promoting role in the tumor immune microenvironment, and they are also associated with poor prognosis. This paper reviews the mechanisms and stimulating factors of macrophages in the process of colorectal cancer metastasis and intends to indicate that targeting macrophages may be a promising strategy in colorectal cancer treatment.

show abstract

Tumour‐associated macrophage‐derived DOCK7‐enriched extracellular vesicles drive tumour metastasis in colorectal cancer via the RAC1/ABCA1 axis

Chen,

Zhou,

Guan

et al. 2024

Clinical & Translational Med

View full text Add to dashboard Cite

BackgroundMetastasis accounts for the majority of deaths among patients with colorectal cancer (CRC). Here, the regulatory role of tumour‐associated macrophages (TAMs) in CRC metastasis was explored.MethodsImmunohistochemical (IHC) analysis of the TAM biomarker CD163 was conducted to evaluate TAM infiltration in CRC. Transwell assays and an ectopic liver metastasis model were established to evaluate the metastatic ability of tumour cells. RNA sequencing (RNA‐seq) and liquid chromatography‒mass spectrometry (LC‒MS) were applied to identify the differentially expressed genes and proteins in CRC cells and in TAM‐derived extracellular vesicles (EVs). Cholesterol content measurement, a membrane fluidity assay and filipin staining were performed to evaluate cholesterol efflux in CRC cells.ResultsOur results showed that TAM infiltration is positively correlated with CRC metastasis. TAMs can facilitate the migration and invasion of MC‐38 and CT‐26 cells via EVs. According to the RNA‐seq data, TAM‐EVs increase cholesterol efflux and enhance membrane fluidity in CRC cells by regulating ABCA1 expression, thus affecting the motility of CRC cells. Mechanistically, DOCK7 packaged in TAM‐EVs can activate RAC1 in CRC cells and subsequently upregulate ABCA1 expression by phosphorylating AKT and FOXO1. Moreover, IHC analysis of ABCA1 in patients with liver‐metastatic CRC indicated that ABCA1 expression is significantly greater in metastatic liver nodules than in primary CRC tumours.ConclusionsOverall, our findings suggest that DOCK7 delivered via TAM‐EVs could regulate cholesterol metabolism in CRC cells and CRC cell metastasis through the RAC1/AKT/FOXO1/ABCA1 axis. DOCK7 could thus be a new therapeutic target for controlling CRC metastasis.

show abstract

Tumor-derived exosomal microRNA-106b-5p activates EMT-cancer cell and M2-subtype TAM interaction to facilitate CRC metastasis

Cited by 109 publications

References 52 publications

Tumour microenvironment: a non-negligible driver for epithelial−mesenchymal transition in colorectal cancer

Tumour microenvironment: a non-negligible driver for epithelial−mesenchymal transition in colorectal cancer

Macrophages, as a Promising Strategy to Targeted Treatment for Colorectal Cancer Metastasis in Tumor Immune Microenvironment

Tumour‐associated macrophage‐derived DOCK7‐enriched extracellular vesicles drive tumour metastasis in colorectal cancer via the RAC1/ABCA1 axis

Contact Info

Product

Resources

About