2021
DOI: 10.1038/s41420-021-00677-9
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Targeting ERK induced cell death and p53/ROS-dependent protective autophagy in colorectal cancer

Abstract: In recent years, many studies have shown that autophagy plays a vital role in the resistance of tumor chemotherapy. However, the interaction between autophagy and cell death has not yet been clarified. In this study, a new specific ERK inhibitor CC90003 was found to suppress colorectal cancer growth by inducing cell death both in vitro and in vivo. Studies have confirmed that higher concentrations of ROS leads to autophagy or cell death. In this research, the role of CC90003-induced ROS was verified. But after… Show more

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Cited by 26 publications
(20 citation statements)
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“…Therefore, we choose the ERK signaling pathway for further study. The ERK pathway is activated in response to increased ROS levels and participates in various cellular processes, including proliferation, migration, and apoptosis, that can also positively affect cancer development [ 28 ] [ 29 ]. Thus, we investigated whether the ROS-ERK1/2 pathway is also involved in the tumorigenicity of G3842A mutant cell.…”
Section: Resultsmentioning
confidence: 99%
“…Therefore, we choose the ERK signaling pathway for further study. The ERK pathway is activated in response to increased ROS levels and participates in various cellular processes, including proliferation, migration, and apoptosis, that can also positively affect cancer development [ 28 ] [ 29 ]. Thus, we investigated whether the ROS-ERK1/2 pathway is also involved in the tumorigenicity of G3842A mutant cell.…”
Section: Resultsmentioning
confidence: 99%
“…The ERK pathway plays a critical role in the regulation of cell proliferation, survival, and differentiation . Previous studies showed that activation of the ERK pathway plays an active role in mediating CDDP-induced apoptosis, , while ERK signaling is a survival mechanism that is critical for CDDP resistance and subsequently promotes autophagy. Furthermore, the ERK signaling activation has been shown to mediate CDDP-related nephrotoxicity , and hematological toxicity . Therefore, to determine the role of ERK in the EVO–Pt­(IV) compound-treated MCF-7 cells, the protein expression and phosphorylation of ERK were detected by immunofluorescence and western blotting.…”
Section: Resultsmentioning
confidence: 99%
“…Through ROS/JNK signaling, photodynamic therapy induces autophagy-mediated cell death in human CRC, and knockdown of ATG5 or ATG7 inhibited the apoptosis of CRC cells by inhibiting the autophagic response after photodynamic therapy ( 78 ). In addition, it has been demonstrated that ERK inhibitors induce autophagy in CRC cells by activating ROS/p53 and cell death simultaneously ( 79 ). In CRC cells, hindering activated ROS-mediated mitochondrial signaling and AMPK/mTOR signaling pathways causes apoptosis and autophagy ( 64 ).…”
Section: Role Of Autophagy In Crcmentioning
confidence: 99%