Evidence map›Paper›PMID 25484078›Full record

ArticleAutophagy2015

Identification of secreted proteins that reflect autophagy dynamics within tumor cells.

Adam A Kraya, Shengfu Piao, Xiaowei Xu, Gao Zhang, Meenhard Herlyn, Phyllis Gimotty, Beth Levine, Ravi K Amaravadi, David W Speicher

Open access · bronzeAbstract read
In one paragraph

Article in Autophagy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers.

0numbers the graph read from it
0cells of the map it votes in
81citing papers in PubMed
6.4field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

81 citing papers in PubMed, 115 citations in OpenAlex.

  1. Article
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  12. Application Value of Antimicrobial Peptides in Gastrointestinal Tumors.International journal of molecular sciences · 2023
    Review
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21 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 5 institutions in 2 countries.

Adam A Krayaa Center for Systems and Computational Biology; The Wistar Institute ; Philadelphia , PA USA.
Shengfu Piao
Xiaowei Xu
Gao Zhang
Meenhard Herlyn
Phyllis Gimotty
Beth Levine
Ravi K Amaravadi
David W Speicher
Philadelphia University · USInstitute of Molecular Biology and Biophysics · RUUniversity of Pennsylvania · USThe University of Texas Southwestern Medical Center · USThe Wistar Institute · US

Funding

UNIVERSITY OF PENNSYLVANIA CAN CTR SUPPORT GRANTP30CA016520 · NCI · UNIVERSITY OF PENNSYLVANIA · PI SHELLEY L BERGER · 1985 to 2026
$222.3M
Tumor Microenvironment and MetastasisP30CA010815 · NCI · WISTAR INSTITUTE · PI Luis J Montaner · 1985 to 2026
$75.9M
Targeting the MAP and PI3 Kinase Pathways in MelanomaP01CA114046 · NCI · WISTAR INSTITUTE · PI HERLYN, MEENHARD F, WEERARATNA, ASHANI T · 2008 to 2023
$37.1M
Targeted Combination Therapy for MelanomaP50CA174523 · NCI · WISTAR INSTITUTE · PI HERLYN, MEENHARD F · 2014 to 2018
$11.1M
Training Program in Computational GenomicsT32HG000046 · NHGRI · UNIVERSITY OF PENNSYLVANIA · PI JUNHYONG KIM, Mingyao Li · 1999 to 2026
$9.5M
Beclin 1-Bcl-2 Interactions: Effects on AutophagyR01CA109618 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI LEVINE, BETH C · 2004 to 2014
$3.1M
Therapeutic approaches that target cancer cell metabolismK23CA120862 · NCI · UNIVERSITY OF PENNSYLVANIA · PI AMARAVADI, RAVI K · 2008 to 2012
$686k
NCI NIH HHS 1K23CA120862NCI NIH HHS CA010815NCI NIH HHS K23 CA120862NCI NIH HHS P01 CA114046NCI NIH HHS P30 CA010815NCI NIH HHS P30 CA016520NCI NIH HHS P50 CA174523NCI NIH HHS R01 CA109618NHGRI NIH HHS 5T32HG000046-15
6 · The paper itself

Abstract

Macroautophagy, a catabolic process of cellular self-digestion, is an important tumor cell survival mechanism and a potential target in antineoplastic therapies. Recent discoveries have implicated autophagy in the cellular secretory process, but potential roles of autophagy-mediated secretion in modifying the tumor microenvironment are poorly understood. Furthermore, efforts to inhibit autophagy in clinical trials have been hampered by suboptimal methods to quantitatively measure tumor autophagy levels. Here, we leveraged the autophagy-based involvement in cellular secretion to identify shed proteins associated with autophagy levels in melanoma. The secretome of low-autophagy WM793 melanoma cells was compared to its highly autophagic metastatic derivative, 1205Lu in physiological 3-dimensional cell culture using quantitative proteomics. These comparisons identified candidate autophagy biomarkers IL1B (interleukin 1, β), CXCL8 (chemokine (C-X-C motif) ligand 8), LIF (leukemia inhibitory factor), FAM3C (family with sequence similarity 3, member C), and DKK3 (dickkopf WNT signaling pathway inhibitor 3) with known roles in inflammation and tumorigenesis, and these proteins were subsequently shown to be elevated in supernatants of an independent panel of high-autophagy melanoma cell lines. Secretion levels of these proteins increased when low-autophagy melanoma cells were treated with the autophagy-inducing tat-BECN1 (Beclin 1) peptide and decreased when ATG7 (autophagy-related 7) was silenced in high-autophagy cells, thereby supporting a mechanistic link between these secreted proteins and autophagy. In addition, serum from metastatic melanoma patients with high tumor autophagy levels exhibited higher levels of these proteins than serum from patients with low-autophagy tumors. These results suggest that autophagy-related secretion affects the tumor microenvironment and measurement of autophagy-associated secreted proteins in plasma and possibly in tumors can serve as surrogates for intracellular autophagy dynamics in tumor cells.

Indexed as

AutophagyAutophagy-Related Protein 7Biomarkers, TumorCell Line, TumorCell ProliferationCulture MediaGene SilencingHumansMelanomaNeoplasm MetastasisNeoplasm ProteinsRNA, Small InterferingSpheroids, CellularUbiquitin-Activating EnzymesATG7 protein, humanAutophagy-Related Protein 7Biomarkers, TumorCulture MediaNeoplasm ProteinsRNA, Small InterferingUbiquitin-Activating EnzymesATG5, autophagy-related 5ATG7, autophagy-related 7autophagyAV, autophagic vacuoleBECN1, Beclin 1, autophagy-relatedbiomarkercancerCXCL8, chemokine (C-X-C motif) ligand 8DKK3, dickkopf WNT signaling pathway inhibitor 3EGF, epidermal growth factorIF, interstitial fluidIL1B, interleukin 1, βLC3/MAP1LC3, microtubule-associated protein 1 light chain 3LIF, leukemia inhibitory factormelanomaM, mediaPtdIns3K, phosphatidylinositol 3-kinaseSAM, significance analysis of microarrayssecretome

Identifiers

PMID25484078
PMCPMC4502670
OpenAlexW2080689345

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.