FSTL1: a double-edged sword in cancer development

Flolistatin-related protein 1 (FSTL1), a secreted glycoprotein that is involved in many physiological functions, has attracted much interest and has been implicated in a wide range of diseases, including heart diseases and inflammatory diseases. In recent years, the involvement of FSTL1 in cancer progression has been implicated and researched. FSTL1 plays a contradictory role in cancer, depending on the cancer type as well as the contents of the tumor microenvironment. As reviewed here, the structure and distribution of FSTL1 are first introduced. Subsequently, the expression and clinical significance of FSTL1 in various types of cancer as a tumor enhancer or inhibitor are addressed. Furthermore, we discuss the functional role of FSTL1 in various processes that involve tumor cell proliferation, metastasis, immune responses, stemness, cell apoptosis, and resistance to chemotherapy. FSTL1 expression is tightly controlled in cancer, and a multitude of cancer-related signaling cascades like TGF-β/BMP/Smad signaling, AKT, NF-κB, and Wnt-β-catenin signaling pathways are modulated by FSTL1. Finally, FSTL1 as a therapeutic target using monoclonal antibodies is stated. Herein, we review recent findings showing the double-edged characteristics and mechanisms of FSTL1 in cancer and elaborate on the current understanding of therapeutic approaches targeting FSTL1.