ATF1 and RAS in exosomes are potential clinical diagnostic markers for cervical cancer

Shi, Yanhua; Wang, Wei; Yang, Bin; Tian, Hongge

doi:10.1002/cbf.3307

Cited by 21 publications

(13 citation statements)

References 32 publications

(48 reference statements)

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“…For example, in cervical cancer models, activating transcription factor 1 (ATF1) and RAS genes were detected in the systemically circulating blood exosomes of the corresponding murine models. Interestingly, this study revealed that ATF1 and RAS genes were found significantly elevated in tumors of primary and recurrent cervical cancer in the mouse model, and they were also detected in the blood exosomes making them excellent biomarkers for cancer monitoring [54]. In the quest for alternative pancreatic cancer diagnostics, mutations in K-Ras and p53 were detected in the exosomal DNA obtained from serum of pancreatic cancer patients as well as established cell lines [55].…”

Section: Oncogenic K-ras In Exosomes and Cancer Diagnosticsmentioning

confidence: 99%

Ras and exosome signaling

Sexton

Mpilla

Kim

et al. 2019

Seminars in Cancer Biology

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Ras gene (HRAS, NRAS, and KRAS) has been observed to be mutated and hyper-activated in a significant proportion of cancers. However, mutant Ras remains a challenging therapeutic target. Similarly, inhibition of targets upstream and downstream of Ras has shown limited clinical utility. There have been attempts to develop and deliver mutant K-Ras silencing RNAs either through their encapsulation in liposomes or nanoparticles. However, these approaches show very limited success due to the lack of stability of such carrier molecules alongside associated toxicity. There is a pressing need for the identification of better therapeutic targets for Ras or its associated pathways as well as improvements in the design of superior RNAi delivery systems to suppress mutant K-Ras. More than a decade ago, it was shown that aggregates of palmitoylated Ras isoforms (H-Ras and N-Ras) passage through the cytosol on rapidly moving nanosized particles (“rasosomes”). Fast forward a decade, considerable new knowledge has emerged in the area of small vesicles, microparticles, and exosomes. Exosomes are tiny vesicles and play a significant role in regulating cancer-related signaling pathways. Exosomes have also been studied as delivery vehicles to transport drugs, proteins, and microRNAs of choice for therapeutic purposes. K-Ras pathway proteins have been implicated in exosome biogenesis and extravasation processes. This review provides an update on the current knowledge related to K-Ras signaling and exosomes and also discusses how these tiny vesicles can be harnessed to successfully deliver the K-Ras silencing moieties.

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Section: Oncogenic K-ras In Exosomes and Cancer Diagnosticsmentioning

confidence: 99%

Ras and exosome signaling

Sexton

Mpilla

Kim

et al. 2019

Seminars in Cancer Biology

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show abstract

“…Wnt/β-catenin, p38/MAPK, p53, and hedgehog signaling pathways were also reported to be related to carcinogenesis and progression in CC [13][14][15][16][17]. In addition, emerging molecules such as circular RNAs (circRNAs), long noncoding RNAs (lncRNAs), and exosomes were also shown to be related to the tumorigenesis of CC [18][19][20]. In recent decades, molecule-targetted therapy of CC has been developed.…”

Section: Introductionmentioning

confidence: 99%

The role of miRNAs in the invasion and metastasis of cervical cancer

Wang

Chen

2019

Bioscience Reports

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Cervical cancer (CC) with early metastasis of the primary tumor results in poor prognosis and poor therapeutic outcomes. MicroRNAs (miRNAs) are small, noncoding RNA molecules that play a substantial role in regulating gene expression post-transcriptionally and influence the development and progression of tumors. Numerous studies have discovered that miRNAs play significant roles in the invasion and metastasis of CC by affecting specific pathways, including Notch, Wnt/β-catenin, and phosphoinositide-3 kinase (PI3K)-Akt pathways. miRNAs also effectively modulate the process of epithelial–mesenchymal transition. Many studies provide new insights into the role of miRNAs and the pathogenesis of metastatic CC. In this review, we will offer an overview and update of our present understanding of the potential roles of miRNAs in metastatic CC.

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“…With the high mortality rate of cervical cancers, more information is needed regarding detection and treatment of the diseased. In this regard, several investigators have begun to examine extracellular vesicles (EVs) and their role in disease protection [2], as disease biomarkers [3][4][5] and/or as a cargo/vaccine agents for cervical cancer [6][7][8][9][10][11][12][13][14][15][16][17][18].…”

Section: Introductionmentioning

confidence: 99%

Alcohol Exposure Impacts the Composition of HeLa-Derived Extracellular Vesicles

et al. 2019

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Extracellular vesicles are nanosized vesicles that are under intense investigation for their role in intercellular communication. Extracellular vesicles have begun to be examined for their role in disease protection and their role as disease biomarkers and/or vaccine agents. The goal of this study was to investigate the effects of alcohol exposure on the biogenesis and composition of extracellular vesicles derived from the cervical cancer line, HeLa. The HeLa cells were cultured in exosome-free media and were either mock-treated (control) or treated with 50 mM or 100 mM of alcohol for 24 h and 48 h. Our results demonstrated that alcohol significantly impacts HeLa cell viability and exosome biogenesis/composition. Importantly, our studies demonstrate the critical role of alcohol on HeLa cells, as well as HeLa-derived extracellular vesicle biogenesis and composition. Specifically, these results indicate that alcohol alters extracellular vesicles’ packaging of heat shock proteins and apoptotic proteins. Extracellular vesicles serve as communicators for HeLa cells, as well as biomarkers for the initiation and progression of disease.

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ATF1 and RAS in exosomes are potential clinical diagnostic markers for cervical cancer

Cited by 21 publications

References 32 publications

Ras and exosome signaling

Ras and exosome signaling

The role of miRNAs in the invasion and metastasis of cervical cancer

Alcohol Exposure Impacts the Composition of HeLa-Derived Extracellular Vesicles

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