Back to Search
Start Over
PDCD6 cooperates with C-Raf to facilitate colorectal cancer progression via Raf/MEK/ERK activation
- Source :
- Journal of Experimental & Clinical Cancer Research : CR, Journal of Experimental & Clinical Cancer Research, Vol 39, Iss 1, Pp 1-15 (2020)
- Publication Year :
- 2020
-
Abstract
- Background Colorectal cancer (CRC) is one of the most common malignancies, and it’s expected that the CRC burden will substantially increase in the next two decades. New biomarkers for targeted treatment and associated molecular mechanism of tumorigenesis remain to be explored. In this study, we investigated whether PDCD6 plays an oncogenic role in colorectal cancer and its underlying mechanism. Methods Programmed cell death protein 6 (PDCD6) expression in CRC samples were analyzed by immunohistochemistry and immunofluorescence. The prognosis between PDCD6 and clinical features were analyzed. The roles of PDCD6 in cellular proliferation and tumor growth were measured by using CCK8, colony formation, and tumor xenograft in nude mice. RNA-sequence (RNA-seq), Mass Spectrum (MS), Co-Immunoprecipitation (Co-IP) and Western blot were utilized to investigate the mechanism of tumor progression. Immunohistochemistry (IHC) and quantitative real-time PCR (qRT-PCR) were performed to determine the correlation of PDCD6 and MAPK pathway. Results Higher expression levels of PDCD6 in tumor tissues were associated with a poorer prognosis in patients with CRC. Furthermore, PDCD6 increased cell proliferation in vitro and tumor growth in vivo. Mechanistically, RNA-seq showed that PDCD6 could affect the activation of the MAPK signaling pathway. PDCD6 interacted with c-Raf, resulting in the activation of downstream c-Raf/MEK/ERK pathway and the upregulation of core cell proliferation genes such as MYC and JUN. Conclusions These findings reveal the oncogenic effect of PDCD6 in CRC by activating c-Raf/MEK/ERK pathway and indicate that PDCD6 might be a potential prognostic indicator and therapeutic target for patients with colorectal cancer.
- Subjects :
- 0301 basic medicine
MAPK/ERK pathway
Male
Cancer Research
Colorectal cancer
MAP Kinase Signaling System
Mice, Nude
Apoptosis
Growth
medicine.disease_cause
lcsh:RC254-282
03 medical and health sciences
Mice
0302 clinical medicine
Downregulation and upregulation
medicine
Biomarkers, Tumor
Tumor Cells, Cultured
Animals
Humans
c-Raf
Cell Proliferation
Mice, Inbred BALB C
business.industry
Cell growth
Research
Calcium-Binding Proteins
Middle Aged
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
medicine.disease
Prognosis
Xenograft Model Antitumor Assays
PDCD6
Gene Expression Regulation, Neoplastic
Proto-Oncogene Proteins c-raf
Survival Rate
030104 developmental biology
Oncology
Tumor progression
030220 oncology & carcinogenesis
Cancer research
MAPK signaling pathway
Female
Carcinogenesis
business
Apoptosis Regulatory Proteins
Colorectal Neoplasms
Subjects
Details
- ISSN :
- 17569966
- Volume :
- 39
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Journal of experimentalclinical cancer research : CR
- Accession number :
- edsair.doi.dedup.....6dcaaf23ba22a80fab286b5a4c31776d