{Reference Type}: Journal Article
{Title}: Pro-survival signaling regulates lipophagy essential for multiple myeloma resistance to stress-induced death.
{Author}: Peng P;Chavel C;Liu W;Carlson LM;Cao S;Utley A;Olejniczak SH;Lee KP;
{Journal}: Cell Rep
{Volume}: 43
{Issue}: 7
{Year}: 2024 Jul 3
暂无{DOI}: 10.1016/j.celrep.2024.114445
{Abstract}: Pro-survival metabolic adaptations to stress in tumorigenesis remain less well defined. We find that multiple myeloma (MM) is unexpectedly dependent on beta-oxidation of long-chain fatty acids (FAs) for survival under both basal and stress conditions. However, under stress conditions, a second pro-survival signal is required to sustain FA oxidation (FAO). We previously found that CD28 is expressed on MM cells and transduces a significant pro-survival/chemotherapy resistance signal. We now find that CD28 signaling regulates autophagy/lipophagy that involves activation of the Ca2+→AMPK→ULK1 axis and regulates the translation of ATG5 through HuR, resulting in sustained lipophagy, increased FAO, and enhanced MM survival. Conversely, blocking autophagy/lipophagy sensitizes MM to chemotherapy in vivo. Our findings link a pro-survival signal to FA availability needed to sustain the FAO required for cancer cell survival under stress conditions and identify lipophagy as a therapeutic target to overcome treatment resistance in MM.