Plasma-derived extracellular vesicle proteins as a source of biomarkers for lung adenocarcinoma

Vykoukal, Jody; Sun, Nan; Aguilar-Bonavides, Clemente; Katayama, Hiroyuki; Tanaka, Ichidai; Fahrmann, Johannes F.; Capello, Michela; Fujimoto, Junya; Aguilar, Mitzi; Wistuba, Ignacio I.; Taguchi, Ayumu; Ostrin, Edwin J.; Hanash, Samir M.

doi:10.18632/oncotarget.20748

Cited by 71 publications

(64 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…However, by employing palmitoyl proteomics, many abundant EV proteins are depleted, so we are able to identify these low abundant nuclear proteins. These nuclear proteins include several proteins that have been proposed as drivers and liquid biopsy markers for cancer including CSE1L 53 and HUWE1 54 . Furthers studies to understand how these proteins are incorporated into EVs may yield important insights into cancer progression.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive palmitoyl-proteomic analysis identifies distinct protein signatures for large and small cancer-derived extracellular vesicles

Mariscal

Vagner

Kim

et al. 2019

Preprint

View full text Add to dashboard Cite

Extracellular vesicles (EVs) are membrane-enclosed particles that play an important role in cancer progression and have emerged as a promising source of circulating biomarkers. Protein S-acylation, also known as palmitoylation, has been proposed as a post-translational mechanism that modulates the dynamics of EV biogenesis and protein cargo sorting. However, technical challenges have limited large-scale profiling of the whole palmitoyl-proteins of EVs. We successfully employed a novel approach that combines low-background acyl-biotinyl exchange (LB-ABE) with label-free proteomics to analyze the palmitoyl proteome of large EVs (L-EVs) and small EVs (S-EVs) from prostate cancer cells. Here we report the first palmitoyl-protein signature of EVs, and demonstrate that L-and S-EVs harbor proteins associated with distinct biological processes and subcellular origin. We identified STEAP1, STEAP2, and ABBC4 as prostate cancer-specific palmitoyl proteins enriched in both EV populations in comparison with the originating cell lines. Importantly, the presence of the above proteins in EVs was significantly reduced upon inhibition of palmitoylation in the producing cells. These results suggest that palmitoylation may be involved in the differential sorting of proteins to distinct EV populations and allow for better detection of disease biomarkers.

show abstract

Section: Discussionmentioning

confidence: 99%

Comprehensive palmitoyl-proteomic analysis identifies distinct protein signatures for large and small cancer-derived extracellular vesicles

Mariscal

Vagner

Kim

et al. 2019

Preprint

View full text Add to dashboard Cite

show abstract

“…SRGN is a small molecule glycoprotein predominantly distributed in the cell cytoplasm and cell membrane; however, it can also be secreted and integrated into the extracellular matrix [22]. SRGN can be derived and utilized in exosomes to promote tumor growth and metastasis in multiple myeloma [23] and lung adenocarcinoma [24]; however, its role in CRC exosomes remains to be elucidated. Furthermore, considering a possible association between SRGN expression and its invasive potential, we suggest that SRGN may have severe impacts on mesenchymal cells or the surrounding tumor cells and necessitate further studies.…”

Section: Discussionmentioning

confidence: 99%

SRGN Promotes Colorectal Cancer Metastasis as a Critical Downstream Target of HIF-1α

Yang

et al. 2018

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: The chondroitin sulfate proteoglycan serglycin (SRGN), a hematopoietic cell granule proteoglycan, has been implicated in promoting tumor metastasis; however, the underlying mechanisms remain to be elucidated. The present study aimed to investigate the SRGN gene expression and its regulation as downstream signaling of hypoxia-inducible transcription factor 1 alpha (HIF-1α) in colorectal cancer (CRC) cells and tissues. Methods: The expression of SRGN was analyzed in CRC specimens for its correlation with progression and metastasis. Using chromatin-immunoprecipitation (ChIP), quantitative real-time PCR, Western blot, and transwell assay, the functional role and underlying mechanism of SRGN in CRC metastasis were elucidated. Thus, this study provides evidence of a critical role of SRGN in metastatic progression of CRC. Results: Our results indicated that SRGN overexpression was significantly associated with poor prognosis in CRC specimens. SRGN overexpression promoted CRC cell migration and invasion in vitro; however, SRGN depletion exhibited contrasting effects. Mechanistic investigations revealed that HIF-1α regulated SRGN transcription via physically binding to a hypoxia response element in its promoter region. Conclusions: In conclusion, we demonstrated that dysregulated HIF-1α/SRGN signaling promotes CRC progression and metastasis. SRGN may serve as a potential candidate therapeutic target for metastatic CRC.

show abstract

“…Given that it is the leading cause of cancer‐related death worldwide, and there are currently no specific proteins that can distinguish between the various histological subtypes in their early stages, the identification of novel biomarkers for NSCLC is urgently needed . One of the first studies to profile the proteome of plasma‐derived EVs from patients with NSCLC went to great lengths to identify bona fide EV proteins . A novel single‐step density gradient flotation EV isolation workflow was described, and protein abundance was measured using total spectral counts for each protein on the linear trap quadrupole (LTQ)‐Orbitrap XL mass spectrometer.…”

Section: Plasmamentioning

confidence: 99%

Tumor‐Derived Extracellular Vesicles as a Novel Source of Protein Biomarkers for Cancer Diagnosis and Monitoring

Ruhen

Meehan

2019

Proteomics

View full text Add to dashboard Cite

“Liquid biopsies” have received attention as a complementary tool for traditional tissue biopsies that may enhance the spectrum of analysis for tumor‐derived factors. One such factor gaining prominence in the liquid biopsy field is extracellular vesicles (EVs), membrane‐bound nanovesicles which are secreted by cells into biofluids such as blood, urine, and saliva. EVs are released in both physiological and pathological conditions and can transport a variety of molecules, including proteins, metabolites, RNA, microRNAs, and DNA, to distant sites throughout the body. As such, they are emerging as a promising source of tumor biomarkers for the noninvasive diagnosis, prognosis, and monitoring of cancer patients. In particular, the wealth of tumor‐related information that can be gleaned from the EV proteomic cargo has become apparent through mass spectrometric analysis, which has provided new benchmarks for clinically focused biomarker research. In this review, the current achievements in the use of MS for identifying potential EV‐derived protein biomarkers of cancer are explored, and the techniques and challenges involved in this pursuit are summarized.

show abstract

Plasma-derived extracellular vesicle proteins as a source of biomarkers for lung adenocarcinoma

Cited by 71 publications

References 35 publications

Comprehensive palmitoyl-proteomic analysis identifies distinct protein signatures for large and small cancer-derived extracellular vesicles

Comprehensive palmitoyl-proteomic analysis identifies distinct protein signatures for large and small cancer-derived extracellular vesicles

SRGN Promotes Colorectal Cancer Metastasis as a Critical Downstream Target of HIF-1α

Tumor‐Derived Extracellular Vesicles as a Novel Source of Protein Biomarkers for Cancer Diagnosis and Monitoring

Contact Info

Product

Resources

About