Together, our findings indicated that SPK1 enhanced tumor growth in lung cancer and induced metastasis by activating the ERK1/2 signaling pathway, indicating its potential application in NSCLC diagnosis and therapy.
The analysis of protein expression in 114 human colorectal cancer tissues demonstrated that the expressions of SphK1, FAK, phosphorylated (p)‑FAK, E‑cadherin and vimentin were associated with the metastasis of colorectal cancer.
SIGNIFICANCE: SPHK1 is overexpressed in TNBC and promotes metastasis, targeting SPHK1 or its downstream target NFκB with clinically available inhibitors could be effective for inhibiting TNBC metastasis.
Statistical analyses revealed that high levels of SPHK1 expression were associated with tumor size, lymph node metastasis and the Tumor-Node-Metastasis stage.
High SPHK1 expression was significantly associated with aggressive CRC behavior and worse overall survival, and was an independent predictor of distant metastasis.
Moreover, the metabolism of ceramide for S1P biosynthesis, which is mediated by sphingosine kinase 1 and 2, and its role in influencing cancer cell growth, drug resistance and tumour metastasis through S1PR-dependent or receptor-independent signalling are highlighted.
Previous studies suggested that sphingosine-1-phosphate produced by sphingosine kinase 1, which is activated by phosphorylation, plays important roles in the progression of disease and metastasis.
The present study aimed to systematically assess the roles of SPHK1 in thyroid carcinoma metastasis and further investigate the possible underlying mechanisms.
In summary, the findings suggested that hispidulin suppressed tumor growth and metastasis by inhibiting the Sphk1 activity and consequently modulating ceramide-S1P rheostat.
Here, we reported that SPHK1 induced the epithelial-mesenchymal transition (EMT) by accelerating CDH1/E-cadherin lysosomal degradation and facilitating the invasion and metastasis of HepG2 cells.
Immunohistochemical analysis of 122 breast cancer cases revealed that the expression levels of SPHK1 were upregulated in 64 tumor tissues (52.5%), and increased expression levels of the protein were significantly associated with the presence of lymph node metastasis (P=0.0016), number of positive lymph nodes (P=0.0268) and presence of distant metastasis (P=0.0097).
Our data suggest that SPHK1 is involved in the development and progression of breast cancer and can serve as a potential predictive biomarker of distant metastasis and patient outcome.
We previously demonstrated that SPHK1 is overexpressed and associated with clinical stage, locoregional recurrence, distant metastasis and poor prognosis in nasopharyngeal carcinoma (NPC).
Previous studies suggested that S1P produced by sphingosine kinase 1 (SphK1) in breast cancer plays important roles in progression of disease and metastasis.
The importance of stromal SPHK1 in tumorigenesis was confirmed in vivo, by demonstrating a significant reduction of tumor growth and metastasis in SPHK1 knockout mice.
Sphingosine kinase 1 (SK1) is a key regulator of the dynamic ceramide/sphingosine 1-phosphate rheostat balance and important in the pathological cancer genesis, progression, and metastasis processes.
There was a close correlation between the expression of SphK1 and FAK or p-FAK and the co-expression of SphK1, FAK and p-FAK significantly associated with histological grade, Dukes' stage, lymph node metastasis and distant metastasis.
Here we report pharmacologic evidence of a critical role for sphingosine kinase 1 (SphK1) in producing S1P and mediating tumor-induced hemangiogenesis and lymphangiogenesis in a murine model of breast cancer metastasis.