Can dehydroepiandrostenedione (DHEA) target PRL-3 to prevent colon cancer metastasis?

Jyotsna Sundar,Munirathinam Gnanasekar

doi:10.1016/j.mehy.2013.01.033

Jyotsna Sundar, Munirathinam Gnanasekar

Open Access

https://doi.org/10.1016/j.mehy.2013.01.033

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Abstract

Colorectal cancer (CRC) is a frequently diagnosed cancer and causing significant mortality in the patients. Metastasis caused by CRC is mainly responsible for this cancer-related deaths. Despite recent advancements in the treatment methods, prognosis remains poor. Therefore, effective treatment strategies need to be designed for successful management of this disease. Dehydroepiandrostenedione (DHEA), a 17-ketosteroid hormone produced by adrenal glands, gonads and including gastrointestinal tract is required for several physiological processes. Deregulation of DHEA levels leads to various disease conditions including cancer. In fact, several experimental studies strongly suggest that DHEA could be used as a chemopreventive agent against colon cancer. Prenlyation of certain membrane proteins such as phosphatase of regenerating liver-3 (PRL-3) is crucial for metastatic progression of colon cancer cells. The ability of DHEA to target prenylation pathway could be utilized to inhibit PRL-3 prenylation for successful prevention of CRC metastases. As DHEA is a widely consumed drug for various ailments, incorporation of DHEA in the treatment regimen may be beneficial to prevent or delay the occurrence of metastasis resulting from CRC.

Highlights

Colorectal cancer (CRC) is a frequently diagnosed cancer and causing significant mortality in the patients
Consistent genetic alterations associated with the transition from primary colorectal cancers to liver metastases was studied by Saha et al [3] who performed the serial analysis of gene expression profiles
The specific substrate for phosphatase of regenerating liver-3 (PRL-3) in vivo has not been clearly identified, it has been addressed in prior studies about the importance of the protein tyrosine phosphatase (PTP) domain in promoting cancer cell growth, invasion and metastasis [8], The other functional domain of PRL-3 is the CCVM motif for prenylation

Summary

Introduction

Colorectal cancer (CRC) is a frequently diagnosed cancer and causing significant mortality in the patients. The specific substrate for PRL-3 in vivo has not been clearly identified, it has been addressed in prior studies about the importance of the PTP domain in promoting cancer cell growth, invasion and metastasis [8], The other functional domain of PRL-3 is the CCVM motif for prenylation. The CAAX prenylation motif present in the c-terminal region of PRL-3 protein (Figure 1) has shown to be important for membrane interaction of PRL3 thereby enabling their participation in various signal transduction pathways [5].

Results

Conclusion