Hypoxia induced deregulation of sphingolipids in colon cancer is a prognostic marker for patient outcome.

Sphingolipids are important for the physicochemical properties of cellular membranes and deregulated in tumors. In human colon cancer tissue ceramide synthase (CerS) 4 and CerS5 are reduced which correlates with a reduced survival probability of late-stage colon cancer patients. Both enzymes are reduced after hypoxia in advanced colorectal cancer (CRC) cells (HCT-116, SW620) but not in non-metastatic CRC cells (SW480, Caco-2).

T-Cell-Specific CerS4 Depletion Prolonged Inflammation and Enhanced Tumor Burden in the AOM/DSS-Induced CAC Model.

To better understand the role of sphingolipids in the multifactorial process of inflammatory bowel disease (IBD), we elucidated the role of CerS4 in colitis and colitis-associated cancer (CAC). For this, we utilized the azoxymethane/dextran sodium sulphate (AOM/DSS)-induced colitis model in global CerS4 knockout (CerS4 KO), intestinal epithelial (CerS4 Vil/Cre), or T-cell restricted knockout (CerS4 LCK/Cre) mice. CerS4 KO mice were highly sensitive to the toxic effect of AOM/DSS, leading to a high mortality rate.

Mouse Liver Compensates Loss of Sgpl1 by Secretion of Sphingolipids into Blood and Bile.

Sphingosine 1 phosphate (S1P) lyase () catalyses the irreversible cleavage of S1P and thereby the last step of sphingolipid degradation. Loss of in humans and mice leads to accumulation of sphingolipids and multiple organ injuries. Here, we addressed the role of hepatocyte for regulation of sphingolipid homoeostasis by generating mice with hepatocyte-specific deletion of ( mice).

Ceramide Synthase 5 Deficiency Aggravates Dextran Sodium Sulfate-Induced Colitis and Colon Carcinogenesis and Impairs T-Cell Activation.

Ceramide synthase 5 is one of six enzymes that catalyze the production of ceramides from sphingosine or sphinganine. Ceramides are important components of cell membranes and act as signaling molecules. Previously it has been shown that ceramide synthase 6 and 2 influence colitis in several animal models with sometimes opposite effects.

The Lipid Status in Patients with Ulcerative Colitis: Sphingolipids are Disease-Dependent Regulated.

The factors that contribute to the development of ulcerative colitis (UC), are still not fully identified. Disruption of the colon barrier is one of the first events leading to invasion of bacteria and activation of the immune system. The colon barrier is strongly influenced by sphingolipids.

Ceramide synthases in cancer therapy and chemoresistance.

Drug resistance is one major reason for failure of cancer therapy. In the past 10 years, evidence emerged showing that ceramides of specific chain length, generated by six different ceramide synthases (CerS), are deregulated in different cancer types thereby influencing chemosensitivity. In this review we sum up the cellular mechanisms regulated by CerS and the respective ceramides of specific chain length contributing to chemoresistance and how we can interfere with these mechanisms to overcome drug resistance by targeting CerS.