Br J Cancer: LIMK2-mediated SPOP phosphate degradation promotes the development of descending resistance to prostate cancer

Prostate cancer (PCa) is still the most common type of urological cancer, ranking second in the United States in male cancer-related deaths.
191,930 new cases and 33,330 projected deaths in the United States by 2020.
although androgen deprivation therapy can be effective in treating the disease, almost all tumors eventually develop into deadly desopathic resistance PCa (CRPC).
3,4, it is urgent to explore the molecular mechanisms associated with CRPC morbidity in order to identify effective drug targets.
SPOP as an important E3 ubiganic connective enzyme, which can act as a tumor suppressor or tumor initiator.
in PCa, it inhibits tumor occurrence by degrading several carcinogenic substrates.
SPOP is the most mutated gene in PCa (about 15%), which invalidates the protein and promotes cancer.
PCA tumors that have retained wild-type SPAP can still develop into CRPC, indicating that there are other important regulatory mechanisms to reduce the expression of SPAP.
previous studies have shown that expression levels of SPOP decreased by about 94 percent in prostate tumors carrying wild SPOP, but it is not clear how the molecular mechanisms are associated with the reduction.
the study identified THESPOP as the direct target of LIMK2 by using LIMK2 to directly phosphate SPAP and regulating its nuclear positioning.
the relationship between SPAP and LIMK2 and their carcinogenic effects were detected through a variety of bio-chemical analysis methods.
also further validated the relationship at the body level through transplant tumor experiments.
researchers found that LIMK2 can degrade SPOP by directly phosphoricizing three bits of SPOP, which in turn promotes the ubibiturization of LIMK2, thus forming a feedback loop.
degradation of SPOP strengthens the carcinogenic effects of AR, ARv7 and c-Myc.
further studies show that antiphosphorylation SPOP can completely inhibit the occurrence of tumors in the body, indicating that LIMK2-mediated SPAP degradation is a key event in the development of PCa.
LIMK2-SPOP signaling pathrapy affects the relevant models of CRPC onset, the results show that patients with gene mutation SPOP tumors need corresponding gene therapy strategies, and the relationship between LIMK2-SPOP also shows that by inhibiting LIMK2 to maintain wild type SPOP or can inhibit the development of the disease.
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