Evidence map›Paper›PMID 30367545›Full record

ArticleMolecular oncology2019

Hypoxia-driven paracrine osteopontin/integrin αvβ3 signaling promotes pancreatic cancer cell epithelial-mesenchymal transition and cancer stem cell-like properties by modulating forkhead box protein M1.

Junyu Cao, Jie Li, Liankang Sun, Tao Qin, Ying Xiao, Ke Chen, Weikun Qian, Wanxing Duan, Jianjun Lei, Jiguang Ma and 2 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular oncology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
51citing papers in PubMed, 1 pooled it
5.1field-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

51 citing papers in PubMed, 1 synthesis or guideline pooled it, 94 citations in OpenAlex.

  1. Pooled it
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  14. Integrins in cancer stem cells.Frontiers in cell and developmental biology · 2024
    Review
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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

12 authors at 1 institution in 1 country.

Junyu CaoDepartment of Hepatobiliary Surgery, First Affiliated Hospital, Xi'an Jiaotong University, China.ORCID 0000-0003-0123-5656
Jie LiDepartment of Hepatobiliary Surgery, First Affiliated Hospital, Xi'an Jiaotong University, China.
Liankang SunDepartment of Hepatobiliary Surgery, First Affiliated Hospital, Xi'an Jiaotong University, China.
Tao QinDepartment of Hepatobiliary Surgery, First Affiliated Hospital, Xi'an Jiaotong University, China.
Ying XiaoDepartment of Hepatobiliary Surgery, First Affiliated Hospital, Xi'an Jiaotong University, China.
Ke ChenDepartment of Hepatobiliary Surgery, First Affiliated Hospital, Xi'an Jiaotong University, China.
Weikun QianDepartment of Hepatobiliary Surgery, First Affiliated Hospital, Xi'an Jiaotong University, China.
Wanxing DuanDepartment of Hepatobiliary Surgery, First Affiliated Hospital, Xi'an Jiaotong University, China.
Jianjun LeiDepartment of Hepatobiliary Surgery, First Affiliated Hospital, Xi'an Jiaotong University, China.
Jiguang MaDepartment of Anesthesiology, First Affiliated Hospital, Xi'an Jiaotong University, China.
Qingyong MaDepartment of Hepatobiliary Surgery, First Affiliated Hospital, Xi'an Jiaotong University, China.
Liang HanDepartment of Hepatobiliary Surgery, First Affiliated Hospital, Xi'an Jiaotong University, China.
First Affiliated Hospital of Xi'an Jiaotong University · CN

Funding

National Natural Scientific Foundation of China 81502074National Natural Scientific Foundation of China 81572734National Natural Scientific Foundation of China 81672434National Natural Scientific Foundation of China 81702916
6 · The paper itself

Abstract

Pancreatic stellate cells (PSCs), a key component of the tumor microenvironment, contribute to tumor invasion, metastasis, and chemoresistance. Osteopontin (OPN), a phosphorylated glycoprotein, is overexpressed in pancreatic cancer. However, OPN expression in PSCs and its potential roles in tumor-stroma interactions remain unclear. The present study first showed that OPN is highly expressed and secreted in activated PSCs driven by hypoxia, and this process is in a ROS-dependent manner; in addition, OPN was shown to be involved in the PSC-induced epithelial-mesenchymal transition (EMT) and cancer stem cell (CSC)-like properties of pancreatic cancer cells (PCCs). Mechanistically, OPN from activated PSCs interacts with the transmembrane receptor integrin αvβ3 on PCCs to upregulate forkhead box protein M1 (FOXM1) expression and induce malignant phenotypes of PCCs. Moreover, the Akt and Erk pathways participate in OPN/integrin αvβ3 axis-induced FOXM1 expression of PCCs. Our further analysis showed that OPN and FOXM1 are significantly upregulated in pancreatic cancer tissues and are associated with poor clinical outcome, indicating that OPN and FOXM1 might be considered as diagnostic and prognostic biomarkers for patients with pancreatic cancer. In conclusion, we show here for the first time that OPN promotes the EMT and CSC-like properties of PCCs by activating the integrin αvβ3-Akt/Erk-FOXM1 cascade in a paracrine manner, suggesting that targeting the tumor microenvironment represents a promising therapeutic strategy in pancreatic cancer.

Indexed as

Epithelial-Mesenchymal TransitionParacrine CommunicationTumor HypoxiaAdultCell Line, TumorExtracellular Signal-Regulated MAP KinasesFemaleForkhead Box Protein M1HumansIntegrin alphaVbeta3MaleMiddle AgedNeoplastic Stem CellsOsteopontinPancreatic NeoplasmsPancreatic Stellate CellsExtracellular Signal-Regulated MAP KinasesForkhead Box Protein M1Integrin alphaVbeta3OsteopontinProto-Oncogene Proteins c-aktReactive Oxygen Speciescancer stem cell-like propertiesepithelial-mesenchymal transitionhypoxiapancreatic cancerpancreatic stellate cells

Identifiers

PMID30367545
PMCPMC6360359
OpenAlexW2898239497

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.