Upregulation of PAG1/Cbp contributes to adipose-derived mesenchymal stem cells promoted tumor progression and chemoresistance in breast cancer

Lu, Yin; Yang, Yongbo; Liu, Yan; Hao, Yajuan; Zhang, Yijian; Hu, Yunping; Jiang, Lin; Gong, Yurong; Wu, Kangning; Liu, Yingbin

doi:10.1016/j.bbrc.2017.10.118

Cited by 26 publications

(21 citation statements)

References 43 publications

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“…Our results reinforce previous reports indicating that ASC promote cancer progression [4, 6] and resistance of cancer cells to chemotherapeutics in cell culture settings [16, 20]. We demonstrate that an experimental drug D-CAN, which reduces the numbers of ASC in tumors [10], suppresses the EMT-associated attributes of cancer aggressiveness in cell culture and in mice.…”

Section: Resultssupporting

confidence: 91%

Adipose stromal cell targeting suppresses prostate cancer epithelial-mesenchymal transition and chemoresistance

Ahn

Saha

et al. 2018

Oncogene

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Fat tissue, overgrowing in obesity, promotes the progression of various carcinomas. Clinical and animal model studies indicate that adipose stromal cells (ASC), the progenitors of adipocytes, are recruited by tumors and promote tumor growth as tumor stromal cells. Here, we investigated the role of ASC in cancer chemoresistance and invasiveness, the attributes of tumor aggressiveness. By using human cell co-culture models, we demonstrate that ASC induce epithelial-mesenchymal transition (EMT) in prostate cancer cells. Our results for the first time demonstrate that ASC interaction renders cancer cells more migratory and resistant to docetaxel, cabazitaxel, and cisplatin chemotherapy. To confirm these findings in vivo, we compared cancer aggressiveness in lean and obese mice grafted with prostate tumors. We show that obesity promotes EMT in cancer cells and tumor invasion into the surrounding fat tissue. A hunter-killer peptide D-CAN, previously developed for targeted ASC ablation, suppressed the obesity-associated EMT and cancer progression. Importantly, cisplatin combined with D-CAN was more effective than cisplatin alone in suppressing growth of mouse prostate cancer allografts and xenografts even in non-obese mice. Our data demonstrate that ASC promote tumor aggressiveness and identify them as a target of combination cancer therapy.

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Section: Resultssupporting

confidence: 91%

Adipose stromal cell targeting suppresses prostate cancer epithelial-mesenchymal transition and chemoresistance

Ahn

Saha

et al. 2018

Oncogene

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“…TMEM132C is reported to be act as the promising diagnostic and prognostic markers in breast cancer [26]. PAG1 is also demonstrated to stimulate tumor progression and chemoresistance of breast cancer [27].…”

Section: Discussionmentioning

confidence: 99%

WITHDRAWN: Identification of a novel lncRNA‑miRNA‑mRNA competing endogenous RNA network associated with prognosis of breast cancer

Wan

Hao

et al. 2020

Preprint

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Background: Breast cancer is one of the most common malignant tumors. Recently, the effects of competing endogenous RNA (ceRNA) on molecular biological mechanism of cancer has aroused great interext. However, research on the pathogenesis and biomarkers of breast cancer is still limited. Thus, this study is aimed to identify the competing endogenous RNA (ceRNA) network related to prognosis of patients with breast cancer.Methods: The RNA SEQ data and corresponding clinical information were downloaded from the Cancer Genome Atlas (TCGA) database, and the difference analysis was performed after data quality control.The similarity between two groups of genes with traits in the network was analyzed by weighted correlation network analysis (WGCNA) . Next, the interaction among lncRNA, miRNA, and mRNA was predicted using miRcode, TargetScan, miRDB, and miRTarBase database, and the lncRNA-miRNA-mRNA ceRNA network was constructed. Finally, the survival model of target mRNA was established by Cox regression analysis.Results: In total 5056 differentially expressed lncRNAs, 712 differentially expressed miRNAs, and 9878 differentially expressed mRNAs were identified. WGCNA predicted that 823 lncRNAs and 1813 mRNAs were closely related to the breast cancer. The lncRNA-miRNA-mRNA ceRNA network involved in breast cancer was constructed with 27 lncRNA, 14 miRNAs and 4 mRNAs. The AUC of four survival models of target mRNA (ZC3H12B + HRH1 + TMEM132C + PAG1) was 0.609, which suggested the sensitivity and specificity of prognosis prediction of breast cancer.Conclusion: This study provides insight into the ceRNA network involved in breast cancer biology, which significantly associated with gene regulation and prognosis of breast cancer. BackgroundBreast cancer, the most frequently diagnosed malignancy in women, remains the second reason for cancer-related in female around the world [1]. It is reported that there are three major therapies for breast cancer, including chemotherapy, endocrine therapy, and targeted therapy [2]. Breast cancer, a heterogeneous disease, varies greatly among different patients and even within each individual patient [3]. Although the survival rate has gradually increased due to the early detection and

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“…ASCs has proven to favor tumor growth in several experimental cancer models, playing a central role in regulating tumor invasiveness and metastatic potential through several mechanisms, such as the paracrine release of exosomes containing pro-oncogenic molecules and the induction of epithelial-mesenchymal transition [2,4,5,6,7,8,9,10,11].…”

Section: Introductionmentioning

confidence: 99%

Concise Review: Adipose-Derived Stem Cells (ASCs) and Adipocyte-Secreted Exosomal microRNA (A-SE-miR) Modulate Cancer Growth and proMote Wound Repair

Gentile

Garcovich

2019

JCM

121

112

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Adipose-derived stem cells (ASCs) have been routinely used from several years in regenerative surgery without any definitive statement about their potential pro-oncogenic or anti-oncogenic role. ASCs has proven to favor tumor progression in several experimental cancer models, playing a central role in regulating tumor invasiveness and metastatic potential through several mechanisms, such as the paracrine release of exosomes containing pro-oncogenic molecules and the induction of epithelial-mesenchymal transition. However, the high secretory activity and the preferential tumor-targeting make also ASCs a potentially suitable vehicle for delivery of new anti-cancer molecules in tumor microenvironment. Nanotechnologies, viral vectors, drug-loaded exosomes, and micro-RNAs (MiR) represent additional new tools that can be applied for cell-mediated drug delivery in a tumor microenvironment. Recent studies revealed that the MiR play important roles in paracrine actions on adipose-resident macrophages, and their dysregulation has been implicated in the pathogenesis of obesity, diabetes, and diabetic complications as wounds. Numerous MiR are present in adipose tissues, actively participating in the regulation of adipogenesis, adipokine secretion, inflammation, and inter-cellular communications in the local tissues. These results provide important insights into Adipocyte-secreted exosomal microRNA (A-SE-MiR) function and they suggest evaluating the potential role of A-SE-MiR in tumor progression, the mechanisms underlying ASCs-cancer cell interplay and clinical safety of ASCs-based therapies.

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Upregulation of PAG1/Cbp contributes to adipose-derived mesenchymal stem cells promoted tumor progression and chemoresistance in breast cancer

Cited by 26 publications

References 43 publications

Adipose stromal cell targeting suppresses prostate cancer epithelial-mesenchymal transition and chemoresistance

Adipose stromal cell targeting suppresses prostate cancer epithelial-mesenchymal transition and chemoresistance

WITHDRAWN: Identification of a novel lncRNA‑miRNA‑mRNA competing endogenous RNA network associated with prognosis of breast cancer

Concise Review: Adipose-Derived Stem Cells (ASCs) and Adipocyte-Secreted Exosomal microRNA (A-SE-miR) Modulate Cancer Growth and proMote Wound Repair

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