FSTL1 promotes growth and metastasis in gastric cancer by activating AKT related pathway and predicts poor survival

Accumulating evidence on the role of Follistatin-like protein 1 (FSTL1) in tumorigenesis and cancer progression is conflicting. Nevertheless, the underlying mechanisms by which FSTL1 contributes to gastric cancer (GC) remain unknown. This study shows that FSTL1 was frequently upregulated in primary GC tissues and significantly correlated with infiltrating depth, lymph node metastasis, unfavorable tumor stage and poor prognosis of GC. Down or up-regulation of FSTL1 inhibited or increased, respectively, the proliferation by reducing apoptosis, clonogenicity, migration and invasion of GC cells in vitro. Moreover, the higher expression of FSTL1 promoted subcutaneous xenograft tumor growth and lung/liver tumor metastasis in vivo. Furthermore, we demonstrate that FSTL1 is involved in regulation of the AKT signaling through analyzing databases and experimental results. Mechanistic studies showed that FSTL1 promoted proliferation, migration and invasion in GC, at least partially, by activating AKT via regulating TLR4/CD14. In all, this study highlights the role of the FSTL1-TLR4/CD14-AKT axis, which provided novel insights into the mechanism of growth and metastasis in GC for the first time.

Automated summary

The role of Follistatin-like protein 1 (FSTL1) in tumorigenesis and cancer progression is conflicting. Nevertheless, this study shows that FSTL1 is frequently upregulated in primary GC tissues and significantly correlated with the progression and poor prognosis of gastric cancer. FSTL1 contributes to GC proliferation, migration, and invasion by regulating the AKT signaling pathway.