Galectin-1 induces metastasis and epithelial-mesenchymal transition (EMT) in human ovarian cancer cells via activation of the MAPK JNK/p38 signalling pathway

摘要

Background: It has been reported that Galectin-1 (Gal-1) indicates bad prognosis of patients with ovarian cancer, and Gal-1 overexpression promotes metastasis of ovarian cancer cells. Nevertheless, the underlying mechanisms of the Gal-1-mediated enhancement of metastasis are still unclear. Furthermore, little is known about whether Gal-1 affects epithelial-mesenchymal transition (EMT) in ovarian cancer. Methods: The human SKOV3-ip and SKOV3 cell lines were transfected with Gal-1 siRNAs and LV-Gal-1 lentivirus, respectively. Cell migration and cell invasion abilities were examined by transwell assays. Protein or mRNA levels of Gal-1, p-JNK1/2, t-JNK1/2, p-p38, t-p38 and EMT markers were detected via immunohistochemistry, qRT-PCR and western blot in SKOV3-ip as well as SKOV3 cells. A xenograft tumour model was used in vivo to ascertain whether upregulation of Gal-1 in ovarian cancer cells can enhance metastasis in vivo. Results: In a total of 107 human ovarian cancer tissues, higher Gal-1 expression strongly associated with higher histological grade, more lymph node metastases and more advanced FIGO stage, while lower E-cadherin expression strongly associated with higher histological grade, more lymph node metastases and more advanced FIGO stage. In vitro assays revealed that Gal-1 promoted migration and invasion of ovarian cancer cells, as well as EMT. Additionally, the results showed that Gal-1 enhanced EMT, migration and invasion by activating the MAPK JNK/p38 signalling pathway. Moreover, in vivo bioluminescence imaging revealed that Gal-1 modulated ovarian cancer metastasis in nude mice. Immunochemistry of xenograft tumour tissues confirmed that Gal-1 may modulate metastasis and EMT via the MAPK JNK/p38 signalling pathway. Additionally, treatment of Gal-1 mice with the MAPK JNK/p38 signalling pathway antagonists SB203580 or SP600125 reduced cancer metastasis. Conclusion: Gal-1 enhances metastasis and EMT of ovarian cancer cells via promoting the activation of the MAPK JNK/p38 signalling pathway, suggesting the possibility that Gal-1 is a molecular target to prevent and cure ovarian cancer metastasis.