Prothymosin α promotes colorectal carcinoma chemoresistance through inducing lipid droplet accumulation

•PTMA expression is significantly increased in CRC patients.•PTMA enhances LD accumulation in CRC cells.•PTMA-dependent LD production facilitates CRC chemoresistance.•PTMA promotes chemoresistance by regulating SREBP-1-mediated lipogenesis.•PTMA promotes the acetylation and activation of STAT3 to support LD biogenesis and chemoresistance. Colorectal cancer (CRC) affects millions of people worldwide. Chemoresistance seriously impairs the therapeutic effects. Lipid droplets (LDs) abnormally accumulate in CRC supported chemoresistance. Exploring the mechanism of LD-induced chemoresistance is extremely important for improving prognosis of CRC patients. The expression of PTMA was increased in both CRC tissues and cells, which was positively correlated with LD production. PTMA facilitated chemoresistance to gemcitabine by inducing LD production in CRC cells. PTMA enhanced LD biogenesis and chemoresistance to gemcitabine by promoting SREBP-1-mediated lipogenesis and STAT3 activation in CRC.