Mechanisms of Progranulin Action and Regulation in Genitourinary Cancers - PubMed (original) (raw)

Review

Mechanisms of Progranulin Action and Regulation in Genitourinary Cancers

Ryuta Tanimoto et al. Front Endocrinol (Lausanne). 2016.

Abstract

The growth factor progranulin has emerged in recent years as a critical regulator of transformation in several cancer models, including breast cancer, glioblastomas, leukemias, and hepatocellular carcinomas. Several laboratories, including ours, have also demonstrated an important role of progranulin in several genitourinary cancers, including ovarian, endometrial, cervical, prostate, and bladder tumors, where progranulin acts as an autocrine growth factor thereby modulating motility and invasion of transformed cells. In this review, we will focus on the mechanisms of action and regulation of progranulin signaling in genitourinary cancers with a special emphasis on prostate and bladder tumors.

Keywords: anchorage-independent growth; bladder and prostate cancer; motility; progranulin; tumor formation in vivo.

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Figures

Figure 1

Figure 1

Progranulin signaling in bladder cancer. The schematic draw summarizes the current knowledge of progranulin signaling pathways leading to motility and invasion of bladder cancer cells. Progranulin interaction with the unidentified progranulin membrane receptor mediates progranulin internalization and interaction with the F-actin protein drebrin, thus regulating MAPK and Akt pathways and cytoskeletal remodeling (40). Additionally, progranulin signaling activates paxillin, which may contribute with MAPK in regulating the dynamic of focal adhesions.

Figure 2

Figure 2

Sortilin-dependent regulation of progranulin action in prostate cancer. Sortilin promotes progranulin uptake through clathrin-dependent endocytosis and targets progranulin for degradation in the lysosomes. Sortilin loss is associated with enhanced progranulin levels and action in castration-resistant prostate cancer cells.

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