Osteopontin as a Regulator of Colorectal Cancer Progression and Its Clinical Applications

SIMPLE SUMMARY: The mortality of colorectal cancer is principally related to metastatic disease at the time of diagnosis or to the growth of initially undetectable micro-metastasis. Current therapeutic strategies are efficient in patients with locally advanced cancer, but are rarely able to cure patients with metastatic disease. Therapeutic failure is mainly associated with drug resistance and an aggressive phenotype. The identification of new biomarkers for micro-metastasis and tumor progression remains an unmet clinical need that should allow for improved patient stratification for optimal treatment and may lead to the identification of novel therapeutic targets. Osteopontin (OPN), a multifunctional protein, has emerged as a potentially valuable biomarker in several cancer types. This review principally describes the molecular mechanisms of OPN that are associated with colorectal cancer (CRC) progression and metastasis, as well as the use of OPN as a clinical biomarker. This review identifies a role for OPN as a biomarker ready for extended clinical application and discusses its use as a therapeutic target. ABSTRACT: A high expression of the phosphoprotein osteopontin (OPN) has been associated with cancer progression in several tumor types, including breast cancer, hepatocarcinoma, ovarian cancer, and colorectal cancer (CRC). Interestingly, OPN is overexpressed in CRC and is associated with a poor prognosis linked to invasion and metastasis. Here, we review the regulation and functions of OPN with an emphasis on CRC. We examine how epigenetic and genetic regulators interact with the key signaling pathways involved in this disease. Then, we describe the role of OPN in cancer progression, including proliferation, survival, migration, invasion, and angiogenesis. Furthermore, we outline the interest of using OPN as a clinical biomarker, and discuss if and how osteopontin can be implemented as a routine assay in clinical laboratories for monitoring CRC patients. Finally, we discuss the use of OPN an attractive, but challenging, therapeutic target.