Selenoproteins and Metastasis

Abstract

Cancer survival is largely impacted by the dissemination of cancer cells from the original tumor site to secondary tissues or organs through metastasis. Targets for antimetastatic therapies have recently become a focus of research, but progress will require a better understanding of the molecular mechanisms driving metastasis. Selenoproteins play important roles in many of the cellular activities underlying metastasis including cell adhesion, matrix degradation and migration, invasion into the blood and extravasation into secondary tissues, and subsequent proliferation into metastatic tumors along with the angiogenesis required for growth. In this review the roles identified for different selenoproteins in these steps and how they may promote or inhibit metastatic cancers is discussed. These roles include selenoenzyme modulation of redox tone and detoxification of reactive oxygen species, calcium homeostasis and unfolded protein responses regulated by endoplasmic reticulum selenoproteins, and the multiple physiological responses influenced by other selenoproteins.

Keywords: Angiogenesis; Antioxidant; Calcium flux; Cancer; Migration; Redox; Selenium.

© 2017 Elsevier Inc. All rights reserved.

Figures

Figure 1.

The metastatic process. Metastases are formed via a multi-step process occurring after an initial tumor has been established. During metastasis tumor cells escape their primary site by passage through extracellular matrix and intravasation into blood vessels or entry into lymphatic vessels. They then translocate via systemic circulatory systems protected by platelets (tumor cell embolus, adhesion to basement membrane and extravasation) or they travel to draining lymph nodes. Once in distant tissue they proceed through metastatic deposit, angiogenesis and growth.

Figure 2.

Potential roles for selenoproteins in metastasis. Selenoproteins located in different sites within the cell or in extracellular spaces may promote or inhibit malignant cells as they progress through the steps or metastasis.