Cell Death Differ: DYRK2 activates HSF1 to enhance resistance to protein toxic stress and promote the development of triple negative breast cancer

About 90% of solid tumors and 75% of hemato-made cancers exhibit some degree of non-totality.
previous studies have shown that non-thymosome cells are less adaptable in yeast and mammalian systems than whole-body cells.
cells regulate unbalanced non-methicosomes through protein degradation and folding, and the positive regulatory factors of these pathways are critical to the survival of non-methicocyte cells, which can also be potential targets for cancer treatment.
in order to resist the above-mentioned protein toxicity stress response, cancer cells activated the protein toxic stress response pathway, which is regulated by the transcription factor HSF1 (thermal shock factor 1).
the current development of inhibitors for transcription regulators such as HSF1 remains challenging, identifying and targeting upstream regulators for HSF1 may be a viable alternative treatment strategy.
DYRK2 affects the expression levels of HSF1 target gene HSP70 in this study, the researchers confirmed that in triple negative breast cancer (TNBC) cells, DYRK2 was able to promote its nuclear stability and transcription activity through phosphorylation of HSF1.
knock-out of DYRK2 can reduce the activity of HSF1 and make TNBC cells sensitive to protein toxicity stress.
importantly, in tumors in TNBC patients, the expression level of DYRK2 is positively associated with active HSF1 and is related to the patient's poor prognostics, which also indicates that DYRK2 can promote the development of TNBC.
DYRK2 expression levels were associated with HSF1 nucleation levels and were associated with adverse prognostic and tumor recurrence in TNBC patients, the above findings reveal that DYRK2 is a key regulatory factor for HSF1 transcription and a potential therapeutic target for TNBC.
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