Stromal POSTN induced by TGF-β1 facilitates the migration and invasion of ovarian cancer

Yue, Huiran; Li, Wenzhi; Chen, Ruifang; Wang, Jieyu; Lu, Xin; Li, Jun

doi:10.1016/j.ygyno.2020.11.026

Cited by 99 publications

(81 citation statements)

References 33 publications

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“…We identified seven EMT-related genes (TPM1, LAMC1, POSTN, CCN1, MGP, PCOLCE2, and DPYSL3) with prognostic significance in patients with colon cancer from TCGA and GSE17536 cohorts. The high expression of these seven genes was detrimental to the poor prognosis of patients with digestive tumors [53][54][55][56][57][58][59]. These genes may be associated with the target genes.…”

Section: Discussionmentioning

confidence: 99%

Infiltrating T-cell abundance combined with EMT-related gene expression as a prognostic factor of colon cancer

Huang

Chen

et al. 2021

Bioengineered

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EMT-related gene expression reportedly exhibits correlation with the anti-tumor immunity of T cells. In the present study, we explored the factors that might affect the efficacy of immunotherapy in colon cancer with treatment. In this regard, RNA-seq and clinical data of 469 colon cancer samples derived from the Cancer Genome Atlas (TCGA) database were used to calculate infiltrating T-cell abundance (ITA), to illustrate a pathway enrichment analysis, and to construct Cox proportional hazards (CPH) regression models. Subsequently, the RNA-seq and clinical data of 177 colon cancer samples derived from the GSE17536 cohort were used to validate the CPH regression models. We found that ITA showed correlation with EMT-related gene expression, and that it was not an independent prognostic factor for colon cancer. However, upon comparison of two groups with the same ITA, higher EMT expression helped predicted a worse prognosis, whereas a higher ITA could help predict a better prognosis upon comparison of two groups with the same EMT. Additionally, seven genes were found to be statistically related to the prognosis of patients with colon cancer. These results suggest that the balance between ITA and EMT-related gene expression is conducive to the prognosis of patients with colon cancer, and TPM1 is necessary to further explore the common target genes of immune checkpoint blockade.

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Section: Discussionmentioning

confidence: 99%

Infiltrating T-cell abundance combined with EMT-related gene expression as a prognostic factor of colon cancer

Huang

Chen

et al. 2021

Bioengineered

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“…Periostin expression was reported to be controlled by the TGF-β/Smad pathway, which also, in turn, regulated the TGF-β/Smad pathway ( Blanchard et al, 2008 ; Lorts et al, 2012 ; Noguchi et al, 2016 ; Mitamura et al, 2018 ; Yue et al, 2021 ). TGF-β inhibits the myogenesis process through Smad3 rather than Smad2 ( Liu et al, 2001 ).…”

Section: Resultsmentioning

confidence: 99%

“…Next, we studied how Postn regulated the myogenesis process in DM1. Many studies have revealed that Postn had crosstalk with the TGF-β/Smad pathway ( Blanchard et al, 2008 ; Lorts et al, 2012 ; Noguchi et al, 2016 ; Mitamura et al, 2018 ; Yue et al, 2021 ). TGF-β involved pathway was discovered to inhibit myogenesis and promote myoblast proliferation ( Massague et al, 1986 ; Ge et al, 2011 ).…”

Section: Discussionmentioning

confidence: 99%

“…Postn is well known as an important microenvironment component that favors tumor growth and metastasis. In ovarian cancer, Postn is upregulated by the TGF-β pathway and promotes migration and invasion ( Yue et al, 2021 ). Postn is also a candidate prognostic marker in colorectal cancers ( Oh et al, 2017 ) and promotes colorectal cancer progression through activating YAP / TAZ ( Ma et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

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Inhibition of Postn Rescues Myogenesis Defects in Myotonic Dystrophy Type 1 Myoblast Model

Shen

Liu

Wang

et al. 2021

Front. Cell Dev. Biol.

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Myotonic dystrophy type 1 (DM1) is an inherited neuromuscular disease caused by expanded CTG repeats in the 3′ untranslated region (3′UTR) of the DMPK gene. The myogenesis process is defective in DM1, which is closely associated with progressive muscle weakness and wasting. Despite many proposed explanations for the myogenesis defects in DM1, the underlying mechanism and the involvement of the extracellular microenvironment remained unknown. Here, we constructed a DM1 myoblast cell model and reproduced the myogenesis defects. By RNA sequencing (RNA-seq), we discovered that periostin (Postn) was the most significantly upregulated gene in DM1 myogenesis compared with normal controls. This difference in Postn was confirmed by real-time quantitative PCR (RT-qPCR) and western blotting. Moreover, Postn was found to be significantly upregulated in skeletal muscle and myoblasts of DM1 patients. Next, we knocked down Postn using a short hairpin RNA (shRNA) in DM1 myoblast cells and found that the myogenesis defects in the DM1 group were successfully rescued, as evidenced by increases in the myotube area, the fusion index, and the expression of myogenesis regulatory genes. Similarly, Postn knockdown in normal myoblast cells enhanced myogenesis. As POSTN is a secreted protein, we treated the DM1 myoblast cells with a POSTN-neutralizing antibody and found that DM1 myogenesis defects were successfully rescued by POSTN neutralization. We also tested the myogenic ability of myoblasts in the skeletal muscle injury mouse model and found that Postn knockdown improved the myogenic ability of DM1 myoblasts. The activity of the TGF-β/Smad3 pathway was upregulated during DM1 myogenesis but repressed when inhibiting Postn with a Postn shRNA or a POSTN-neutralizing antibody, which suggested that the TGF-β/Smad3 pathway might mediate the function of Postn in DM1 myogenesis. These results suggest that Postn is a potential therapeutical target for the treatment of myogenesis defects in DM1.

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“…Therefore, a high expression level of POSTN, which was experimentally verified to be linked with CAFs [32][33][34] , and a high MIA score for CAFs were simultaneously utilized to define ST clusters of CAFs (Figure S6B). Results showed that CAFs were enriched around some tumor areas in ST slides (Figure 4F), including the hypermetabolic tumor areas of sample TJH34 (Figures 3F&4F).…”

Section: Identification Of a Cluster Of Cancer-associated Fibroblasts (Cafs) In Csccmentioning

confidence: 99%

Single-nucleus RNA Sequencing and Spatial Transcriptomics Reveal the Immunological Microenvironment of Cervical Squamous Cell Carcinoma

Lin

Qiu

et al. 2021

Preprint

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To understand the etiological, structural, and immunological characteristics of cervical squamous cell carcinoma (CSCC), we conducted single nucleus RNA sequencing (snRNA-seq) and spatial transcriptomics (ST) experiments for cervical samples from 20 individuals. When exploring the possible factors shaping the intra-individual immune heterogeneity in CSCC, we identified a cluster of cancer-associated fibroblasts (CAFs) enriched around some tumors, which highly expressed ACTA2, POSTN, ITGB4, and FAP. Results showed that the CAFs might support the growth and metastasis of tumors by inhibiting lymphocyte infiltration and remodeling the tumor extracellular matrix. Moreover, high CAF signals predicted poorer clinical outcomes for CSCC patients. Our data also revealed the infection profiles of HPV in tumors, the critical factors involved in the progression of cervical cancerous lesions, and the association between tumor metabolism and immune response intensity. Collectively, our findings may improve the prognostic and therapeutic methods for CSCC.

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Stromal POSTN induced by TGF-β1 facilitates the migration and invasion of ovarian cancer

Cited by 99 publications

References 33 publications

Infiltrating T-cell abundance combined with EMT-related gene expression as a prognostic factor of colon cancer

Infiltrating T-cell abundance combined with EMT-related gene expression as a prognostic factor of colon cancer

Inhibition of Postn Rescues Myogenesis Defects in Myotonic Dystrophy Type 1 Myoblast Model

Single-nucleus RNA Sequencing and Spatial Transcriptomics Reveal the Immunological Microenvironment of Cervical Squamous Cell Carcinoma

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