Dataset Information

Endoplasmic reticulum ribosome-binding protein 1, RRBP1, promotes progression of colorectal cancer and predicts an unfavourable prognosis.

ABSTRACT:

Background

Ribosome-binding protein 1 (RRBP1) has been implicated in the regulation of unfolded protein response, which is involved in almost every aspect of cancer development. We aimed to explore the significance of RRBP1 in the progression and prognosis of colorectal cancer (CRC).

Methods

The study population consisted of 856 patients with stage I-III CRC from two hospitals. RRBP1 expression was examined by immunohistochemistry (IHC) in colorectal tissues. The correlation of RRBP1 expression and CRC occurrence was assessed in paired cancer-adjacent tissues. Factors contributing to prognosis were evaluated in a training-validation design with univariate and multivariate Cox analysis. Colorectal cancer aggressiveness caused by RRBP1 knockdown or overexpression was evaluated in CRC cells.

Results

RRBP1 was aberrantly overexpressed in CRC. Compared with low-RRBP1 patients, high-RRBP1 patients had shorter disease-specific survival in the training (hazard ratio (HR), 2.423; 95% confidence interval (CI), 1.531-3.835) and validation cohorts (HR, 3.749; 95% CI, 2.166-6.448) in multivariate Cox analysis. High-RRBP1 independently predicted a shorter disease-free survival (HR, 4.821; 95% CI, 3.220-7.218) in the validation cohort. RRBP1 knockdown reduced the aggressiveness of CRC cells in vitro and inhibited the growth of CRC xenografts in vivo.

Conclusions

High RRBP1 expression facilitates CRC progression and predicts an unfavourable post-operative prognosis.

SUBMITTER: Pan Y

PROVIDER: S-EPMC4559827 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature

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Publications

Endoplasmic reticulum ribosome-binding protein 1, RRBP1, promotes progression of colorectal cancer and predicts an unfavourable prognosis.

Pan Y Y Cao F F Guo A A Chang W W Chen X X Ma W W Gao X X Guo S S Fu C C Zhu J J

British journal of cancer 20150721 5

<h4>Background</h4>Ribosome-binding protein 1 (RRBP1) has been implicated in the regulation of unfolded protein response, which is involved in almost every aspect of cancer development. We aimed to explore the significance of RRBP1 in the progression and prognosis of colorectal cancer (CRC).<h4>Methods</h4>The study population consisted of 856 patients with stage I-III CRC from two hospitals. RRBP1 expression was examined by immunohistochemistry (IHC) in colorectal tissues. The correlation of RR ...[more]

PMID: 26196185

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Project description:BackgroundLong-term accumulation of misfolded proteins leads to endoplasmic reticulum (ER) stress in colorectal cancer (CRC). However, the precise pathways controlling the decision between survival and apoptosis in CRC are unclear. Therefore, in this study, we investigated the function and molecular mechanism of glucosidase I (GCS1) in regulating ER stress in CRC.MethodsA public database was used to confirm the expression level of GCS1 in CRC and normal tissues. Clinical samples from our center were used to confirm the mRNA and protein expression levels of GCS1. Cell proliferation, migration, invasion, and apoptosis assays revealed the biological role of GCS1. Immunohistochemical techniques were used to evaluate the expression of key proteins in subcutaneous implanted tumors in nude mice, which provided further evidence for the biological function of GCS1 in promoting cancer in vivo. The results of coimmunoprecipitation-mass spectrometry analysis and immunofluorescence colocalization analysis the interaction between GCS1 and GRP78. In addition, the mechanism of action of USP10, GRP78, and GCS1 at the post- translational level was investigated. Finally, a tissue microarray was used to examine the connection between GCS1 and GRP78 expression and intracellular localization of these proteins using immunohistochemistry and immunofluorescence.ResultsThe experimental results revealed that GCS1 was substantially expressed in CRC, with higher expression indicating a worse prognosis. Thus, GCS1 can enhance the proliferation and metastasis while inhibiting the apoptosis of CRC cells both in vivo and in vitro. Mechanistically, GCS1 binds to GRP78, recruits USP10 for deubiquitination of GRP78 to promote its degradation, and decreases ER stress-mediated apoptosis, increasing CRC cell proliferation and metastasis.ConclusionsIn summary, GCS1 stimulates CRC growth and migration and reduces ER stress-mediated apoptosis via USP10-mediated deubiquitination of GRP78. Our findings identify a possible therapeutic target for CRC.

Dataset Information

Endoplasmic reticulum ribosome-binding protein 1, RRBP1, promotes progression of colorectal cancer and predicts an unfavourable prognosis.

Background

Methods

Results

Conclusions

Publications

Endoplasmic reticulum ribosome-binding protein 1, RRBP1, promotes progression of colorectal cancer and predicts an unfavourable prognosis.

Similar Datasets

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