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Sphingosine 1-Phosphate Signaling and Metabolism in Chemoprevention and Chemoresistance in Colon Cancer

Department of Biotechnology, University of Rijeka, Radmile Matejčić 2, 51000 Rijeka, Croatia
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Academic Editors: Krešimir Pavelić and Sandra Kraljevic Pavelic
Molecules 2020, 25(10), 2436; https://doi.org/10.3390/molecules25102436
Received: 10 April 2020 / Revised: 8 May 2020 / Accepted: 11 May 2020 / Published: 23 May 2020
(This article belongs to the Special Issue Translational Approach to Antitumor Drugs)
Colorectal carcinoma (CRC) is the leading cause of cancer-related deaths worldwide. Despite advances in prevention and treatment modalities for CRC, rapidly developing resistance to chemotherapy limits its effectiveness. For that reason, it is important to better understand the mechanisms that undergird the process of chemoresistance to enable design of novel anticancer agents specifically targeting malignant properties of cancer cells. Over recent decades, bioactive sphingolipid species have come under the spotlight for their recognized role in cancer development and progression, and the evidence has surfaced to support their role as regulators of anti-cancer drug resistance. Colon cancer is characterized by a shift in sphingolipid balance that favors the production and accumulation of oncogenic species such as sphingosine 1-phosphate (S1P). S1P is known to govern the processes that facilitate cancer cell growth and progression including proliferation, survival, migration, invasion and inflammation. In this review paper, we will give a comprehensive overview of current literature findings on the molecular mechanisms by which S1P turnover, transport and signaling via receptor-dependent and independent pathways shape colon cancer cell behavior and influence treatment outcome in colon cancer. Combining available modulators of S1P metabolism and signaling with standard chemotherapy drugs could provide a rational approach to achieve enhanced therapeutic response, diminish chemoresistance development and improve the survival outcome in CRC patients. View Full-Text
Keywords: colon cancer; chemoresistance; sphingosine 1-phosphate; sphingolipid metabolism; sphingosine kinases colon cancer; chemoresistance; sphingosine 1-phosphate; sphingolipid metabolism; sphingosine kinases
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Grbčić, P.; Sedić, M. Sphingosine 1-Phosphate Signaling and Metabolism in Chemoprevention and Chemoresistance in Colon Cancer. Molecules 2020, 25, 2436.

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