Epithelial–Mesenchymal Plasticity in Tumor Immune Evasion

Mullins, Riley; Pal, Ananya; Barrett, Thomas F.; Neal, Molly Heft; Puram, Sidharth V.

doi:10.1158/0008-5472.can-21-4370

Cited by 30 publications

(39 citation statements)

References 183 publications

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“…Under physiological conditions, Epithelial to mesenchymal transition (EMT) occupy a signi cant position in embryogenesis, cancer, brosis progression and tissue remodeling and all that [23][24][25]. Recent data have pointed out that EMT has been deemed to serves a substantial role in hepatic brosis progression for a long time [5].…”

Section: Discussionmentioning

confidence: 99%

Circ_0072088 mediates hepatic fibrosis renders epithelial to mesenchymal transition through miR-330-3p/CDK1 axis in AML12 hepatocytes

Liu

Xing

Jin

et al. 2022

Preprint

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Hepatic fibrosis was one of the causes to hepatocellular cancer (HCC), owing to limited therapeutic options. And hepatocytes can induce liver fibrogenesis via epithelial-mesenchymal transition (EMT). Multiple circRNAs exert critical role in the occurrence of liver fibrosis via working as microRNA (miRNA) sponges. Circ_0072088 is upregulated in hepatocellular cancer (HCC) and promote proliferation, migration of HCC cells. However, the potential research mechanism for circ_0072088 action against the fibrotic progression remain still unknown. The treatment of AML12 hepatocytes with TGF-β1 contributed to dramatically increased in the levels of circ_0072088. Additionally, in terms of mechanism, circ_0072088 was authenticated to function as miR-330-3p sponge, not only noticeable increase EMT, but also induced fibrosis in AML12 hepatocytes. MiR-330-3p could weaken the roles of circ_0072088 acceleration. Moreover, we proved that CDK1, a miR-330-3p target, was time-dependently augmented in the TGF-β1 treated AML12 hepatocytes, and its overexpression weakens the miR-330-3p regulatory effects.Our findings provided a unique role of the circ_0072088 mediates hepatic fibrosis renders epithelial-mesenchymal transition at least partially through miR-330-3p/CDK1 axis, thus suggesting its tremendous therapeutic potential in the treatment of liver diseases.

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Section: Discussionmentioning

confidence: 99%

Circ_0072088 mediates hepatic fibrosis renders epithelial to mesenchymal transition through miR-330-3p/CDK1 axis in AML12 hepatocytes

Liu

Xing

Jin

et al. 2022

Preprint

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“…Both types of migration are simultaneously present in many cancers [21]. In cancer progression, the plastic changes of numerous cancer cells are shown by morphological and phenotypical conversions, such as EMT and its reverse process the mesenchymal-epithelial transition (MET) [22], the collective-amoeboid transition (CAT) [23], the mesenchymal-amoeboid transition (MAT) [24]. Among these conversions, EMT has been increasingly…”

Section: Local Invasionmentioning

confidence: 99%

“…Deciphering and Targeting Epigenetics in Cancer Metastasis DOI: http://dx.doi.org/10.5772/intechopen.106584 considered a crucial and indispensable stage in the cancer metastatic process over the last decade [22], despite the studies of Seyfried et al in the VM mouse model of systemic metastasis suggesting that EMT is unnecessary for the initial cancer metastasis [25,26].…”

Section: Overview Of Metastatic Cascade During Metastatic Progression...mentioning

confidence: 99%

“…Moreover, increasing emerging evidence shows the potent roles in invasion and EMT of many long noncoding RNAs (lncRNAs), such as lncRNA MEG3, lncRNA PNUTS, and lncRNA MIR100HG [28][29][30]. During this process, cells lost epithelial characteristics and markers like E-cadherin and cytokeratin, instead of gaining mesenchymal characteristics and markers like vimentin, N-cadherin, and fibronectin [22]. In addition to cancer metastasis, EMT has been involved in different cancer stages, including cancer initiation, malignant progression, cancer stemness, and drug resistance [31].…”

Section: Overview Of Metastatic Cascade During Metastatic Progression...mentioning

confidence: 99%

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Deciphering and Targeting Epigenetics in Cancer Metastasis

Huang¹,

Lu²,

Liang³

2023

Cancer Metastasis - Molecular Mechanism and Clinical Therapy

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Once cancer metastasizes to distant organs like the bone, liver, lung, and brain, it is in an advanced stage. Metastasis is a major contributor to cancer-associated deaths. Countless molecules and complex pathways are involved in the dissemination and colonization of cancer cells from a primary tumor at metastatic sites. Establishing the biological mechanisms of the metastatic process is crucial in finding open therapeutic windows for successful interventions. Emerging evidence suggested a variety of epigenetic regulations were identified to regulate cancer metastasis. Here we summarize the procedures and routes of cancer metastasis as well as the roles of epigenetics including ncRNA, DNA methylation, and histone modifications in common metastases. Then we further discuss the potentials and limitations of epigenetics-related target molecules in diagnosis, therapy, and prognosis.

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“…Tumor cell signatures were defined by single cell RNA-sequencing (scRNA-seq) and were related to epithelial differentiation, cell cycle, cell stress, hypoxia, and a partial epithelial-mesenchymal transition (pEMT) [10]. EMT is a trans-differentiation program co-opted by tumor cells that fosters dissemination, stemness features, immune evasion, and treatment resistance [11][12][13][14][15][16]. scRNA-seq resulted in a refinement of the four molecular subtypes identified in TCGA to a malignant-basal subtype incorporating tumors with a partial EMT signature (pEMT), a classical, and an atypical subtype.…”

Section: Introductionmentioning

confidence: 99%

A transcriptomic map of EGFR-induced epithelial-to-mesenchymal transition identifies prognostic and therapeutic targets for head and neck cancer

et al. 2022

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Background Epidermal growth factor receptor (EGFR) is both a driver oncogene and a therapeutic target in advanced head and neck squamous cell carcinoma (HNSCC). However, response to EGFR treatment is inconsistent and lacks markers for treatment prediction. This study investigated EGFR-induced epithelial-to-mesenchymal transition (EMT) as a central parameter in tumor progression and identified novel prognostic and therapeutic targets, and a candidate predictive marker for EGFR therapy response. Methods Transcriptomic profiles were analyzed by RNA sequencing (RNA-seq) following EGFR-mediated EMT in responsive human HNSCC cell lines. Exclusive genes were extracted via differentially expressed genes (DEGs) and a risk score was determined through forward feature selection and Cox regression models in HNSCC cohorts. Functional characterization of selected prognostic genes was conducted in 2D and 3D cellular models, and findings were validated by immunohistochemistry in primary HNSCC. Results An EGFR-mediated EMT gene signature composed of n = 171 genes was identified in responsive cell lines and transferred to the TCGA-HNSCC cohort. A 5-gene risk score comprising DDIT4, FADD, ITGB4, NCEH1, and TIMP1 prognosticated overall survival (OS) in TCGA and was confirmed in independent HNSCC cohorts. The EGFR-mediated EMT signature was distinct from EMT hallmark and partial EMT (pEMT) meta-programs with a differing enrichment pattern in single malignant cells. Molecular characterization showed that ITGB4 was upregulated in primary tumors and metastases compared to normal mucosa and correlated with EGFR/MAPK activity in tumor bulk and single malignant cells. Preferential localization of ITGB4 together with its ligand laminin 5 at tumor-stroma interfaces correlated with increased tumor budding in primary HNSCC tissue sections. In vitro, ITGB4 knock-down reduced EGFR-mediated migration and invasion and ITGB4-antagonizing antibody ASC8 impaired 2D and 3D invasion. Furthermore, a logistic regression model defined ITGB4 as a predictive marker of progression-free survival in response to Cetuximab in recurrent metastatic HNSCC patients. Conclusions EGFR-mediated EMT conveyed through MAPK activation contributes to HNSCC progression upon induction of migration and invasion. A 5-gene risk score based on a novel EGFR-mediated EMT signature prognosticated survival of HNSCC patients and determined ITGB4 as potential therapeutic and predictive target in patients with strong EGFR-mediated EMT.

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Epithelial–Mesenchymal Plasticity in Tumor Immune Evasion

Cited by 30 publications

References 183 publications

Circ_0072088 mediates hepatic fibrosis renders epithelial to mesenchymal transition through miR-330-3p/CDK1 axis in AML12 hepatocytes

Circ_0072088 mediates hepatic fibrosis renders epithelial to mesenchymal transition through miR-330-3p/CDK1 axis in AML12 hepatocytes

Deciphering and Targeting Epigenetics in Cancer Metastasis

A transcriptomic map of EGFR-induced epithelial-to-mesenchymal transition identifies prognostic and therapeutic targets for head and neck cancer

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