Evidence map›Paper›PMID 29569766›Full record

ArticleCell proliferation2018

Lysosomal acid lipase promotes cholesterol ester metabolism and drives clear cell renal cell carcinoma progression.

Jun Wang, Mingyue Tan, Jifu Ge, Ping Zhang, Jie Zhong, Le Tao, Qiong Wang, Xuemei Tong, Jianxin Qiu

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

Article in Cell proliferation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
0.7field-weighted citation impact, top 30% 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

21 citing papers in PubMed, 26 citations in OpenAlex.

  1. Article
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  5. Review
  6. Article
  7. Review
  8. Recent insights into lysosomal acid lipase deficiency.Trends in molecular medicine · 2023
    Review
  9. Review
  10. Article
  11. Review
  12. Article
  13. Review
  14. Article
  15. Review
  16. Article
  17. Review
  18. Obesity, Type 2 Diabetes, and Cancer Risk.Frontiers in oncology · 2020
    Review
  19. Review
  20. Review
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 2 institutions in 2 countries.

Jun WangDepartment of Urology, School of Medicine, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, China.
Mingyue TanDepartment of Urology, School of Medicine, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, China.
Jifu GeDepartment of Urology, School of Medicine, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, China.
Ping ZhangShanghai Key Laboratory for Tumor Microenvironment and Inflammation, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Department of Biochemistry and Molecular Cell Biology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Jie ZhongShanghai Key Laboratory for Tumor Microenvironment and Inflammation, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Department of Biochemistry and Molecular Cell Biology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Le TaoDepartment of Urology, School of Medicine, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, China.
Qiong WangDepartment of Clinical Laboratory, Wuxi People's Hospital Affiliated to Nanjing Medical University, Wuxi, Jiangsu, China.
Xuemei TongShanghai Key Laboratory for Tumor Microenvironment and Inflammation, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Department of Biochemistry and Molecular Cell Biology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Jianxin QiuDepartment of Urology, School of Medicine, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, China.ORCID http://orcid.org/0000-0003-1067-3199
Shanghai Jiao Tong University · CNWuxi People's Hospital · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectivesClear cell renal cell carcinoma (ccRCC) is characterized histologically by accumulation of cholesterol esters, cholesterol and other neutral lipids. Lysosomal acid lipase (LAL) is a critical enzyme involved in the cholesterol ester metabolism. Here, we sought to determine whether LAL could orchestrate metabolism of cholesterol esters in order to promote ccRCC progression. MATERIALS AND

methodsQuantitative reverse-transcription PCR and western blots were conducted to assess the expression of LAL in human ccRCC tissues. We analysed the relationship between LAL levels and patient survival using tissue microarrays. We used cell proliferation assays, colony formation assays, cell death assays, metabolic assays and xenograft tumour models to evaluate the biological function and underlying mechanisms.

resultsLAL was up-regulated in ccRCC tissue. Tissue microarray analysis revealed higher levels of LAL in advanced grades of ccRCC, and high LAL expression indicated lower patient survival. Suppressing LAL expression not only blocked the utilization of cholesterol esters but also impaired proliferation and cellular survival. Furthermore, immunohistochemistry staining showed that LAL expression was correlated with Akt phosphorylation. Suppressing LAL expression decreased the phosphorylation level of Akt and Src and reduced the level of 14,15-epoxyeicosatrienoic acids in ccRCC cells. Supplement of 14,15-epoxyeicosatrienoic acids rescued proliferation in vitro and in vivo.

conclusionsLAL promoted cell proliferation and survival via metabolism of epoxyeicosatrienoic acids and activation of the Src/Akt pathway.

Indexed as

AnimalsArachidonic AcidCarcinoma, Renal CellCell Line, TumorCell ProliferationCholesterol EstersFemaleHumansKaplan-Meier EstimateKidney NeoplasmsMiceMice, Inbred BALB CMice, NudePhosphorylationProto-Oncogene Proteins c-aktRNA InterferenceArachidonic AcidCholesterol EstersProto-Oncogene Proteins c-aktRNA, Small Interferingsrc-Family KinasesSterol Esterase

Identifiers

PMID29569766
PMCPMC6528899
OpenAlexW2794145072

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.