Evidence map›Paper›PMID 29866109›Full record

ArticleJournal of translational medicine2018

Granulin epithelin precursor promotes colorectal carcinogenesis by activating MARK/ERK pathway.

Yi Pan, Siu Tim Cheung, Joanna Hung Man Tong, Ka Yee Tin, Wei Kang, Raymond Wai Ming Lung, Feng Wu, Hui Li, Simon Siu Man Ng, Tony Wing Chung Mak and 2 more

Open access · goldAbstract read
In one paragraph

Article in Journal of translational medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
0.7field-weighted citation impact, top 33% 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

12 citing papers in PubMed, 16 citations in OpenAlex.

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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 2 institutions in 1 country.

Yi PanDepartment of Anatomical and Cellular Pathology, State Key Laboratory in Oncology in South China, Prince of Wales Hospital, The Chinese University of Hong Kong, 30-32 Ngan Shing Street, Shatin, NT, Hong Kong, SAR, China.
Siu Tim CheungDivision of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, SAR, China.
Joanna Hung Man TongDepartment of Anatomical and Cellular Pathology, State Key Laboratory in Oncology in South China, Prince of Wales Hospital, The Chinese University of Hong Kong, 30-32 Ngan Shing Street, Shatin, NT, Hong Kong, SAR, China.
Ka Yee TinDepartment of Anatomical and Cellular Pathology, State Key Laboratory in Oncology in South China, Prince of Wales Hospital, The Chinese University of Hong Kong, 30-32 Ngan Shing Street, Shatin, NT, Hong Kong, SAR, China.
Wei KangDepartment of Anatomical and Cellular Pathology, State Key Laboratory in Oncology in South China, Prince of Wales Hospital, The Chinese University of Hong Kong, 30-32 Ngan Shing Street, Shatin, NT, Hong Kong, SAR, China.
Raymond Wai Ming LungDepartment of Anatomical and Cellular Pathology, State Key Laboratory in Oncology in South China, Prince of Wales Hospital, The Chinese University of Hong Kong, 30-32 Ngan Shing Street, Shatin, NT, Hong Kong, SAR, China.
Feng WuDepartment of Anatomical and Cellular Pathology, State Key Laboratory in Oncology in South China, Prince of Wales Hospital, The Chinese University of Hong Kong, 30-32 Ngan Shing Street, Shatin, NT, Hong Kong, SAR, China.
Hui LiDepartment of Anatomical and Cellular Pathology, State Key Laboratory in Oncology in South China, Prince of Wales Hospital, The Chinese University of Hong Kong, 30-32 Ngan Shing Street, Shatin, NT, Hong Kong, SAR, China.
Simon Siu Man NgInstitute of Digestive Disease, Partner State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, SAR, China.
Tony Wing Chung MakDivision of Colorectal Surgery, Department of Surgery, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, SAR, China.
Ka Fai ToDepartment of Anatomical and Cellular Pathology, State Key Laboratory in Oncology in South China, Prince of Wales Hospital, The Chinese University of Hong Kong, 30-32 Ngan Shing Street, Shatin, NT, Hong Kong, SAR, China. kfto@cuhk.edu.hk.
Anthony Wing Hung ChanDepartment of Anatomical and Cellular Pathology, State Key Laboratory in Oncology in South China, Prince of Wales Hospital, The Chinese University of Hong Kong, 30-32 Ngan Shing Street, Shatin, NT, Hong Kong, SAR, China. awh_chan@cuhk.edu.hk.
Prince of Wales Hospital · CNChinese University of Hong Kong · CN

Funding

Research Grants Council, University Grants Committee CUHK 14104415Research Grants Council, University Grants Committee CUHK 14138016
6 · The paper itself

Abstract

backgroundGranulin epithelin precursor (GEP) is reported to function as a growth factor stimulating proliferation and migration, and conferring chemoresistance in many cancer types. However, the expression and functional roles of GEP in colorectal cancer (CRC) remain elusive. The aim of this study was thus to investigate the clinical significance of GEP in CRC and reveal the molecular mechanism of GEP in CRC initiation and progression.

methodsThe mRNA expression of GEP in CRC cell lines were detected by qRT-PCR. The GEP protein expression was validated by immunohistochemistry in tissue microarray (TMA) including 190 CRC patient samples. The clinicopathological correlation analysis were achieved by GEP expression on TMA. Functional roles of GEP were determined by MTT proliferation, monolayer colony formation, cell invasion and migration and in vivo studies through siRNA/shRNA mediated knockdown assays. The cancer signaling pathway identification was acquired by flow cytometry, western blot and luciferase activity assays.

resultsThe mRNA expression of GEP in CRC was significantly higher than it in normal colon tissues. GEP protein was predominantly localized in the cytoplasm and most of the CRC cases demonstrated abundant GEP protein compared with non-tumorous tissues. GEP overexpression was associated with non-rectal location, advanced AJCC stage, regional lymph node and distant metastasis. By Kaplan-Meier survival analysis, GEP abundance served as a prognostic marker for worse survival in CRC patients. GEP knockdown exhibited anti-cancer effect such as inhibiting cell proliferation, monolayer colony formation, cell invasion and migration in DLD-1 and HCT 116 cells and decelerating xenograft formation in nude mice. siGEP also induced G1 cell cycle arrest and apoptosis. Luciferase activity assays further demonstrated GEP activation was involved in MAPK/ERK signaling pathway.

conclusionIn summary, we compressively delineate the oncogenic role of GEP in colorectal tumorigenesis by activating MAPK/ERK signaling pathway. GEP might serve as a useful prognostic biomarker and therapeutic target for CRC.

Indexed as

MAP Kinase Signaling SystemAdultAgedAged, 80 and overAnimalsApoptosisCarcinogenesisCell Line, TumorColorectal NeoplasmsFemaleG1 Phase Cell Cycle CheckpointsGene Expression Regulation, NeoplasticGranulinsHumansMaleMice, NudeGranulinsRNA, MessengerColorectal cancerGEPMAPK/ERK pathwayOncogene

Identifiers

PMID29866109
PMCPMC5987413
OpenAlexW2806775677

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.