scholarly journals Increased Sphingosine Kinase 1 Expression Predicts Distant Metastasis and Poor Outcome in Patients With Colorectal Cancer

2019 ◽  
Vol 39 (2) ◽  
pp. 663-670 ◽  
Author(s):  
GO EUN BAE ◽  
SUNG-IM DO ◽  
KYUNGEUN KIM ◽  
JI HYUN PARK ◽  
SIHYUN CHO ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Distant Metastasis ◽  
Sphingosine Kinase ◽  
Sphingosine Kinase 1 ◽  
Poor Outcome

MicroRNA-101 down-regulates sphingosine kinase 1 in colorectal cancer cells

2015 ◽  
Vol 463 (4) ◽  
pp. 954-960 ◽  
Author(s):  
Min-Bin Chen ◽  
Lan Yang ◽  
Pei-Hua Lu ◽  
Xing-Li Fu ◽  
Yan Zhang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cells ◽  
Sphingosine Kinase ◽  
Sphingosine Kinase 1 ◽  
Colorectal Cancer Cells

scholarly journals Sphingosine Kinase 1 (SPHK1) Overexpression Contributes to Cetuximab Resistance in Human Colorectal Cancer Models

2012 ◽  
Vol 23 ◽  
pp. ix530
Author(s):  
L. Formisano ◽  
L. Nappi ◽  
R. Rosa ◽  
V. Damiano ◽  
R. Marciano ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Sphingosine Kinase ◽  
Sphingosine Kinase 1 ◽  
Human Colorectal Cancer ◽  
Cancer Models

Role of sphingosine kinase 1 (SphK1) on cetuximab resistance in colorectal cancer models.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e13509-e13509
Author(s):  
Roberto Bianco ◽  
Roberta Rosa ◽  
Lucia Nappi ◽  
Luigi Formisano ◽  
Vincenzo Damiano ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Anticancer Agents ◽  
Acquired Resistance ◽  
Sphingosine Kinase ◽  
Sphingosine Kinase 1 ◽  
Mutational Status ◽  
Resistant Cells

e13509 Background: Although EGFR inhibitors, such as the mAb cetuximab, represent an effective strategy in colorectal cancer (CRC), the clinical use of these agents is limited by intrinsic or acquired resistance. Alterations in the ‘sphingolipid rheostat’, or the balance between the proapoptotic molecule ceramide and the mitogenic factor sphingosine-1-phosphate (S1P), due to overactivation of sphingosine kinase 1 (SphK1), have been involved in the regulation of resistance to anticancer agents. Since some studies described cross-talks between SphK1 and EGFR-dependent signalling pathways, we investigated the contribution of SphK1 to cetuximab resistance in CRC models. Methods: We used CRC cell lines with both intrinsic or acquired resistance to cetuximab. In these models, we analyzed SphK1 expression/activation by using different tools, including the available drug fingolimod (FTY720), both in vitro and in vivo. We confirmed our data through a tissue microarray (TMA)-based analysis on CRC tissues. Results: SphK1 is overexpressed in CRC cells resistant to cetuximab. Higher doses of N,N-dimethylsphingosine (DMS), a potent competitive inhibitor of SphK1, are needed to achieve complete enzyme saturation and survival inhibition in resistant cells. Moreover, ceramide induces apoptosis less efficiently in resistant than in sensitive cells, consistently with the idea that increased SphK1 levels mediate S1P synthesis by ceramide in resistant cells. SphK1 contribution to resistance is supported by the demonstration that SphK1 inhibition by DMS or silencing via siRNA in resistant cells restores sensitivity to cetuximab, whereas exogenous SphK1 overexpression in wild-type cells confers resistance. Re-sensitization to cetuximab is observed after treatment with fingolimod, a S1P receptor inhibitor, both in vitro and in nude mice xenografted with CRC cells. Finally, a TMA-based analysis on CRC tissues revealed that SphK1 expression is related to K-Ras mutational status, a well-known determinant of cetuximab resistance. Conclusions: Our data could clarify the role of SphK1 in the onset of resistance to cetuximab, thus suggesting SphK1 inhibition as a part of novel targeting strategies for resistant cancer patients.

scholarly journals Sphingosine Kinase 1 Overexpression Contributes to Cetuximab Resistance in Human Colorectal Cancer Models

2012 ◽  
Vol 19 (1) ◽  
pp. 138-147 ◽  
Author(s):  
Roberta Rosa ◽  
Roberta Marciano ◽  
Umberto Malapelle ◽  
Luigi Formisano ◽  
Lucia Nappi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Sphingosine Kinase ◽  
Sphingosine Kinase 1 ◽  
Human Colorectal Cancer ◽  
Cancer Models

scholarly journals Sphingosine Kinase 1 and Sphingosine-1-Phosphate Signaling in Colorectal Cancer

2017 ◽  
Vol 18 (10) ◽  
pp. 2109 ◽  
Author(s):  
Yonghua Bao ◽  
Yongchen Guo ◽  
Chenglan Zhang ◽  
Fenghua Fan ◽  
Wancai Yang
Keyword(s):  
Colorectal Cancer ◽  
Sphingosine Kinase ◽  
Sphingosine Kinase 1 ◽  
Sphingosine 1 Phosphate
Sign in / Sign up

Export Citation Format

Share Document