Correlation of PRL3 expression with colorectal cancer progression

Abstract

Objectives: To evaluate the relationship between phosphatase of regenerating liver 3 (PRL3) expression and clinical outcome in colorectal cancer (CRC). Background: PRL3, a protein tyrosine phosphatase functions as one of the key regulatory enzymes of various signal transduction pathways. PRL3 is highly expressed in a majority of cancers and is a novel potential therapeutic target. Methods: PRL3 expression was evaluated by immunohistochemistry in 167 patients with CRC, 37 patients with no disease, and 26 patients with metastatic CRC (mCRC). Phosphorylated Akt at serine 473 (p-Akt S473) expression was also evaluated by immunohistochemistry in mCRC patients. Results: High expression of PRL3 was correlated with CRC progression, and every one unit increase in PRL3 level contributed to an increase in the rate of death by 1%-1.7%. PRL3 expression was significantly higher in liver metastases compared with primary tumors and showed a significant positive correlation with the expression level of p-Akt S473. Conclusion: PRL3 expression levels associated with CRC progression and metastasis, and positively correlated with activated Akt level in mCRC. Together, these findings indicated that PRL3 might be a potential marker for increased risk of CRCspecific tumor burden and identify PRL3 as an attractive therapeutic target for mCRC treatment.

Stathmin expression in metastatic colorectal cancer

“…Furthermore, overexpression of stathmin has been reported to be associated with PI3Kinase activation in endometrial 37 and breast cancers 10 . We have also recently reported the significant positive correlation of PRL3 with activated Akt in metastatic colorectal cancer 5 . MAPK/PI3K and its downstream signaling components are critical for cancer cell proliferation and survival and are identified as hallmarks of cancer 38 .…”

“…10 We have also recently reported the significant positive correlation of PRL3 with activated Akt in metastatic colorectal cancer. 5 MAPK/PI3K and its downstream signaling components are critical for cancer cell proliferation and survival and are identified as hallmarks of cancer. 38 In the present study, we demonstrated that high stathmin expression level positively correlated with Ki67 staining, a cell proliferation marker, and negatively correlated with apoptosis in mCRC.…”

“…We have recently reported phosphatase of regenerating liver 3 (PRL3) as a predictive marker for CRC progression and metastasis 5 . PRL3 is upstream of the phosphatidylinositol‐3 kinase (PI3K)/serine threonine protein kinase Akt signaling pathway, one of the major pathways involved in the invasion and metastatic processes of many cancers including CRC 6‐9 …”

Colorectal cancer: Review of signaling pathways and associated therapeutic strategies

“…However, aberrant PI3K expression in metastatic tumors is not always associated with PIK3CA mutations, suggesting the involvement of other mechanisms. We have identified phosphatase of regenerating liver 3 (PRL3), an upstream marker of the PI3K/Akt pathway, and ezrin, and sodium‐hydrogen exchanger regulatory factor 1 (NHERF1), the downstream markers of PI3K/Akt signaling pathway in CRC 40–42 . These markers are highly expressed in mCRC with minimal expression in normal or premalignant adenoma 40–42 and might be potential targets for anti‐PI3K‐mediated targeted therapy.…”

Colorectal liver metastasis: molecular mechanism and interventional therapy

“…5 ). 140 Since PRL3 transcripts are overexpressed in CRC metastases found in the liver, and PRL3 expression cannot be detected in non-metastatic primary tumors and normal colorectal epithelium. PRL3-induced enhancement of EMT dependent on EGFR activation and PRL3 promoted cell invasion and upregulated MMPS by activating AKT in vitro and in vivo.…”