Evidence map›Paper›PMID 31170987›Full record

ArticleCell communication and signaling : CCS2019

Tumor-secreted PAI-1 promotes breast cancer metastasis via the induction of adipocyte-derived collagen remodeling.

Xiaohui Wei, Sijing Li, Jinyong He, Hongzhi Du, Yang Liu, Wei Yu, Haolin Hu, Lifei Han, Chenfei Wang, Hongyang Li and 5 more

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

Article in Cell communication and signaling : CCS, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.

0numbers the graph read from it
0cells of the map it votes in
50citing papers in PubMed
4.0field-weighted citation impact, top 5% 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

50 citing papers in PubMed, 89 citations in OpenAlex.

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  9. The role of adipogenic niche resident cells in colorectal cancer progression in relation to obesity.Obesity reviews : an official journal of the International Association for the Study of Obesity · 2025
    Review
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  17. Frontiers in cell and developmental biology · 2024
    Article
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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

15 authors at 5 institutions in 1 country.

Xiaohui WeiJiangsu Center for Pharmacodynamics Research and Evaluation, China Pharmaceutical University, No. 24, Tongjiaxiang, Nanjing, China.
Sijing LiJiangsu Key laboratory of Drug Screening, China Pharmaceutical University, No.24, Tongjiaxiang, Nanjing, China.
Jinyong HeJiangsu Key laboratory of Drug Screening, China Pharmaceutical University, No.24, Tongjiaxiang, Nanjing, China.
Hongzhi DuSchool of Pharmacy, Hubei University of Chinese Medicine, Wuhan, China.
Yang LiuJiangsu Center for Pharmacodynamics Research and Evaluation, China Pharmaceutical University, No. 24, Tongjiaxiang, Nanjing, China.
Wei YuJiangsu Center for Pharmacodynamics Research and Evaluation, China Pharmaceutical University, No. 24, Tongjiaxiang, Nanjing, China.
Haolin HuBreast Disease Center, Zhong-Da Hospital, Southeast University, Nanjing, China.
Lifei HanBreast Disease Center, Zhong-Da Hospital, Southeast University, Nanjing, China.
Chenfei WangBreast Disease Center, Zhong-Da Hospital, Southeast University, Nanjing, China.
Hongyang LiInstitute of Dermatology, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.
Xin ShiDepartment of General Surgery, Zhong-Da Hospital, Southeast University, Nanjing, China.
Meixiao ZhanZhuhai Interventional Medical Center, Zhuhai Precision Medical Center, Zhuhai People's Hospital, Zhuhai Hospital of Jinan University, Zhuhai, Guangdong, China.
Ligong LuZhuhai Interventional Medical Center, Zhuhai Precision Medical Center, Zhuhai People's Hospital, Zhuhai Hospital of Jinan University, Zhuhai, Guangdong, China.
Shengtao YuanJiangsu Center for Pharmacodynamics Research and Evaluation, China Pharmaceutical University, No. 24, Tongjiaxiang, Nanjing, China. yuanst@cpu.edu.cn.
Li SunJiangsu Key laboratory of Drug Screening, China Pharmaceutical University, No.24, Tongjiaxiang, Nanjing, China. sunli@cpu.edu.cn.
China Pharmaceutical University · CNZhongda Hospital Southeast University · CNZhuhai People's Hospital · CNChinese Academy of Medical Sciences & Peking Union Medical College · CNHubei University of Chinese Medicine · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundBreast cancer cells recruit surrounding stromal cells, such as cancer-associated fibroblasts (CAFs), to remodel collagen and promote tumor metastasis. Adipocytes are the most abundant stromal partners in breast tissue, local invasion of breast cancer leads to the proximity of cancer cells and adipocytes, which respond to generate cancer-associated adipocytes (CAAs). These cells exhibit enhanced secretion of extracellular matrix related proteins, including collagens. However, the role of adipocyte-derived collagen on breast cancer progression still remains unclear.

methodsAdipocytes were cocultured with breast cancer cells for 3D collagen invasion and collagen organization exploration. Breast cancer cells and adipose tissue co- implanted mouse model, clinical breast cancer samples analysis were used to study the crosstalk between adipose and breast cancer cells in vivo. A combination of proteomics, enzyme-linked immunosorbent assay, loss of function assay, qPCR, western blot, database analysis and chromatin immunoprecipitation assays were performed to study the mechanism mediated the activation of PLOD2 in adipocytes.

resultsIt was found that CAAs remodeled collagen alignment during crosstalk with breast cancer cells in vitro and in vivo, which further promoted breast cancer metastasis. Tumor-derived PAI-1 was required to activate the expression of the intracellular enzyme procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2 (PLOD2) in CAAs. Pharmacologic blockade of PAI-1 or PLOD2 disrupted the collagen reorganization in CAAs. Mechanistically, it was observed that PI3K/AKT pathway was activated in adipocytes upon co-culturing with breast cancer cells or treatment with recombinant PAI-1, which could promote the translocation of transcription factor FOXP1 into the nucleus and further enhanced the promoter activity of PLOD2 in CAAs. In addition, collagen reorganization at the tumor-adipose periphery, as well as the positive relevance between PAI-1 and PLOD2 in invasive breast carcinoma were confirmed in clinical specimens of breast cancer.

conclusionIn summary, our findings revealed a new stromal collagen network that favors tumor invasion and metastasis establish between breast cancer cells and surrounding adipocytes at the tumor invasive front, and identified PLOD2 as a therapeutic target for metastatic breast cancer treatment.

Indexed as

3T3 CellsAdipocytesAdultAnimalsBreast NeoplasmsCell Line, TumorCollagenFemaleForkhead Transcription FactorsHumansMiceMice, Inbred BALB CMice, NudeMiddle AgedNeoplasm MetastasisPhosphatidylinositol 3-KinasesCollagenForkhead Transcription FactorsPhosphatidylinositol 3-KinasesPlasminogen Activator Inhibitor 1Procollagen-Lysine, 2-Oxoglutarate 5-DioxygenaseProto-Oncogene Proteins c-aktBreast CancerCollagenMetastasisMicroenvironmentPAI-1PLOD2

Identifiers

PMID31170987
PMCPMC6554964
OpenAlexW2948079514

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.