Figure 3. Opposing functions of ceramide synthase 1 and 6.

CerS6/C₁₆-ceramide accumulation regulates ER homeostasis and stress responses favoring cell proliferation and tumor growth. Conversely, deduction of CerS6/C₁₆-ceramide by RNAi against CerS6 induces ER stress by the ATF6/CHOP arm, which leads to cell death. CerS1/C₁₈-ceramide levels can be increased by the treatment of chemotherapeutic agents, such as GMZ and DOX, which can inhibit tumor cell growth through the induction of autophagy or by directly inducing tumor cell apoptosis.

CerS: Ceramide synthase; DOX: Doxorubicin; ER: Endoplasmic reticulum;

GMZ: Gemcitabine; HNSCC: Head and neck squamous cell carcinoma.