Biswadeep Sen, Amity University Kolkata
Recent studies show that Inflammation and Carcinogenic processes are interconnected. Not just because both induce DNA instability, but both are driven by the same pathways (like NF-kB, STAT3, mTOR and MAPKs).
The pro-inflammatory cytokines like IL-6, IL-1β, TNF-α and IL-10 mould our immune responses and they are controlled by the pathways mentioned above. Therefore, they can be considered as a double-edged sword, responsible for both our protection and if went wrong, or destruction. Now, these pathways often trigger the UPR which is responsible for cells to survive stress and is initiated by three cellular sensors. These sensors can also trigger the oncogenic pathways leading to malignancy of tumours. UPR is activated whenever an unfolded protein finds itself inside the ER and via autophagy, it helps to eliminate the misfolded proteins. So, we can safely assume that any regulatory problem about it, might trigger a host of diseases including cancer.
Studies have pointed out that ATF6, one of the three sensors of UPR, activated by a mutp53 May contribute to a p38 phosphorylation making it possible for counteracting the autophagy. On the other hand, NF-KB, which is reported to inhibit autophagy, might also be activated by ARF6 and induced by a mutp53. This could contribute to its sustainability of expression level and inhibition of Autophagy.
Therefore, interrupting such interplay between UPR and the oncogenic pathways may affect the pre oncogenic inflammation and stability of a mutp53 and downregulation of them might break the bridge between inflammation and cancer. Several Inhibitors like WP1066 or LY3007113 are used alone or in combination so that they can interfere with the aspects of carcinomic biology.
Also read: Efficient and cost-effective Bacterial mRNA sequencing causing ribosomal RNA depletion
Source: D’Orazi, G., Cordani, M. & Cirone, M. Oncogenic pathways activated by pro-inflammatory cytokines promote mutant p53 stability: a clue for novel anticancer therapies. Cell. Mol. Life Sci. (2020). https://doi.org/10.1007/s00018-020-03677-7
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