β2-adrenoreceptor Signaling Increases Therapy Resistance in Prostate Cancer by Upregulating MCL1.

ABSTRACT: There is accumulating evidence that continuous activation of the sympathetic nervous system due to psychosocial stress increases resistance to therapy and accelerates tumor growth via β2-adrenoreceptor signaling (ADRB2). However, the effector mechanisms appear to be specific to tumor type. Here we show that activation of ADRB2 by epinephrine, increased in response to immobilization stress, delays the loss of MCL1 apoptosis regulator (MCL1) protein expression induced by cytotoxic drugs in prostate cancer cells; and thus, increases resistance of prostate cancer xenografts to cytotoxic therapies. The effect of epinephrine on MCL1 protein depended on protein kinase A (PKA) activity, but was independent from androgen receptor expression. Furthermore, elevated blood epinephrine levels correlated

SUBMITTER: Hassan S 

PROVIDER: S-EPMC8080265 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature