ROS-mediated SRMS activation confers platinum resistance in ovarian cancer

Seeking a better understanding of the non-receptor tyrosine kinase, SRMS

“…Intriguingly, the phosphorylation of OTUB1 at Y26 did not affect the stability of other OTUB1-targeted substrates. In addition, another study conducted by Jiang et al found that SRMS inhibited MKK4 kinase activity via the direct phosphorylation of MKK4 at the Y269 and Y307 residues, resulting in the consequent attenuation of MKK4-JNK activation [ 32 ]. Together, these findings, therefore, suggest that OTUB1 and MKK4 may be substrates of SRMS [ 31 , 32 ].…”

“…Recently, Jiang et al found SRMS to be involved in platinum-based chemotherapy resistance in ovarian cancer [ 32 ]. Ovarian cancer is among the leading cause of mortality in gynecological malignancies, with over 300,000 new diagnoses and over 200,000 deaths in 2020 [ 66 ].…”

“…Jiang et al conducted a kinome-wide synthetic lethal RNAi screening in combination with unbiased data mining in Genomics of Drug Sensitivity in Cancer (GDSC) and Cancer Cell Line Encyclopedia (CCLE) databases of cell line platinum treatment response. They found SRMS to be a novel negative regulator of MKK4-JNK signaling under the platinum therapy [ 32 ]. Additionally, Jiang et al observed that SRMS plays an important role in dictating the efficacy of platinum treatment in ovarian cancer, and the suppression of SRMS was found to sensitize p53-deficient ovarian cancer cells to platinum both in vitro and in vivo [ 32 ].…”

“…They found SRMS to be a novel negative regulator of MKK4-JNK signaling under the platinum therapy [ 32 ]. Additionally, Jiang et al observed that SRMS plays an important role in dictating the efficacy of platinum treatment in ovarian cancer, and the suppression of SRMS was found to sensitize p53-deficient ovarian cancer cells to platinum both in vitro and in vivo [ 32 ]. Furthermore, SRMS suppression led to enhanced MKK4-JNK-mediated apoptosis via the inhibition of MCL1 transcription, increasing platinum efficacy [ 32 ].…”

“…Additionally, Jiang et al observed that SRMS plays an important role in dictating the efficacy of platinum treatment in ovarian cancer, and the suppression of SRMS was found to sensitize p53-deficient ovarian cancer cells to platinum both in vitro and in vivo [ 32 ]. Furthermore, SRMS suppression led to enhanced MKK4-JNK-mediated apoptosis via the inhibition of MCL1 transcription, increasing platinum efficacy [ 32 ]. The team also discovered a small molecule selective inhibitor of B-RafV600E known as PLX4720 to be a novel inhibitor of SRMS.…”