ArticleCancer medicine2021
SphK1-driven autophagy potentiates focal adhesion paxillin-mediated metastasis in colorectal cancer.
Article in Cancer medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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15 citing papers in PubMed, 30 citations in OpenAlex.
- Identification and Validation of a Macrophage Phagocytosis-Related Gene Signature for Prognostic Prediction in Colorectal Cancer (CRC).Current issues in molecular biology · 2025Article
- Gut microbiota interplay with autophagy-EMT dynamics in colorectal cancer.Frontiers in cell and developmental biology · 2025Review
- Sphingosine-1-phosphate stimulates colorectal cancer tumor microenvironment angiogenesis and induces macrophage polarization via macrophage migration inhibitory factor.Frontiers in immunology · 2025Article
- [Sphingosine kinase-1 regulates migration and invasion of gastric cancer cellsNan fang yi ke da xue xue bao = Journal of Southern Medical University · 2024Article
- SPHK1 promotes bladder cancer metastasis via PD-L2/c-Src/FAK signaling cascade.Cell death & disease · 2024Article
- Deciphering the impact of aggregated autophagy-related genes TUBA1B and HSP90AA1 on colorectal cancer evolution: a single-cell sequencing study of the tumor microenvironment.Discover oncology · 2024Article
- SPHK1 potentiates colorectal cancer progression and metastasis via regulating autophagy mediated by TRAF6-induced ULK1 ubiquitination.Cancer gene therapy · 2024Article
- SPHK1 promotes HNSCC immune evasion by regulating the MMP1-PD-L1 axis.Theranostics · 2024Article
- MST4 promotes proliferation, invasion, and metastasis of gastric cancer by enhancing autophagy.Heliyon · 2023Article
- The Role of Paxillin Aberrant Expression in Cancer and Its Potential as a Target for Cancer Therapy.International journal of molecular sciences · 2023Review
- HOXC11 drives lung adenocarcinoma progression through transcriptional regulation of SPHK1.Cell death & disease · 2023Article
- Article
- Prognostic value of autophagy-related genes based on single-cell RNA-sequencing in colorectal cancer.Frontiers in genetics · 2023Article
- Autophagy: A Versatile Player in the Progression of Colorectal Cancer and Drug Resistance.Frontiers in oncology · 2022Review
- SphK1-driven autophagy potentiates focal adhesion paxillin-mediated metastasis in colorectal cancer.Cancer medicine · 2021Article
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12 authors at 1 institution in 1 country.
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Abstract
Invasion and metastasis are the main causes of colorectal cancer (CRC)-related death. Accumulating evidence suggested that sphingosine kinase 1 (SphK1) promoted the metastasis of CRC and autophagy played an important role in SphK1 promoting the metastasis of malignancy. However, the mechanism by which SphK1-driven autophagy promotes invasion and metastasis in CRC remains to be clarified. In the present study, immunohistochemical detection showed the expression of SphK1 and paxillin was higher in human CRC tissues than those of normal colorectal mucosal tissues, they were both associated with TNM staging, lymphatic, and distance metastasis. In addition, study of in situ tumor transplantation model in nude mice showed that the suppression of SphK1 inhibited the growth of colonic orthotopic implantation tumors and the expression of paxillin, p-paxillin, LC3 in the tumor. So, SphK1 may promote CRC metastasis via inducing the expression of paxillin expression and its phosphorylation, in vivo. Furthermore, results of CCK8 assay, transwell and wound healing assays showed that SphK1 promoted the viability, invasion, and metastasis of CRC cells. Transmission electron microscopy detection showed that SphK1 is the key factor in autophagy induction in CRC cells. Moreover, western blot examination indicated that the expression of LC3Ⅱ/Ⅰ, paxillin, p-paxillin, MMP-2, and vimentin was enhanced in SphK1-overexpressed CRC cells and suppressed in SphK1 knockdown CRC cells, meanwhile, the expression of E-cadherin was suppressed in SphK1-overexpressed CRC cells and enhanced in SphK1 knockdown CRC cells. Suppression of autophagy by 3MA reversed the expression of paxillin and its phosphorylation in SphK1-overexpressed CRC cells, indicated that SphK1-driven autophagy induced the expression of paxillin and its phosphorylation in CRC cells. Together, these findings reveal that SphK1-driven autophagy may promote the invasion and metastasis of CRC via promoting the expression of focal adhesion paxillin and its phosphorylation.
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