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

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

J Transl Med

Department 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.

Published: June 2018

AI Article Synopsis

  • The study investigates the role of granulin epithelin precursor (GEP) in colorectal cancer (CRC), focusing on its expression and impact on cancer progression and patient prognosis.
  • Results show that GEP is significantly overexpressed in CRC cells and tissues, correlating with advanced disease stages and poorer survival outcomes.
  • The knockdown of GEP led to reduced cancer cell proliferation and invasiveness, indicating its potential as a therapeutic target through involvement in the MAPK/ERK signaling pathway.

Article Abstract

Background: Granulin 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.

Methods: The 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.

Results: The 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.

Conclusion: In 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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5987413PMC
http://dx.doi.org/10.1186/s12967-018-1530-7DOI Listing

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