Journal
CANCER MEDICINE
Volume 10, Issue 20, Pages 7242-7252Publisher
WILEY
DOI: 10.1002/cam4.4225
Keywords
extracellular domain; FNDC4; HCC; invasion; PI3K; Akt
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Funding
- National Natural Science Foundation of China [81670597, 81972303]
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The study shows that FNDC4, as an extracellular factor, is involved in the invasion and metastasis of HCC, with high expression of FNDC4 correlated with poor survival in patients and promoting migration and invasion of HCC cells. Mechanistically, FNDC4 is related to PI3K/Akt signaling pathway, with its extracellular domain promoting Akt phosphorylation to enhance invasion and metastasis of HCC.
FNDC4 is highly homologous to the exercise-associated myokine FNDC5/irisin, which is highly expressed and promotes the invasion and metastasis of HCC cells. However, the function of FNDC4 remains unknown. Here, we report that FNDC4, an extracellular factor, plays important roles in the invasion and metastasis of HCC. We found that high FNDC4 expression is associated with poor survival in HCC patients and FNDC4 promotes the migration and invasion of HCC cells. Mechanistically, we found that FNDC4 is related to the PI3K/Akt signalling pathway to a certain extent. Specifically, the extracellular domain of FNDC4 acts as an extracellular factor to promote Akt phosphorylation levels in this pathway. These findings reveal that FNDC4 promotes the invasion and metastasis of HCC partly via the PI3K/Akt signalling pathway.
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