Abnormal Phase-separation Behavior And Mechanism Of Action Of GATA3 Mutants In Breast Cancer

Breast cancer is the most common type of female cancer.According to the latest cancer statistics in 2020,the number of new cases has ranked first in all types of cancer,which has aroused widespread concern.GATA3 is the most frequently mutated gene in somatic cells of breast cancer patients,and the research data related to GATA3 need to be further improved.After the mutation of GATA3,the effect of different mutants on the signal pathway,and the morphological changes of protein after the mutation of GATA3,the differences of their biological functions are not clear,and the specific interaction mechanism between GATA3 and ER? needs to be further studied.In this paper,we analyzed the sample data of breast cancer patients to understand the impact of GATA3 on the prognosis of patients.Combined with the potential analysis of GATA3 phase separation,we found that different mutants of GATA3 form different aggregates.Through further study of GATA3 truncated fragments,we determined the key domain of GATA3 phase separation.By combining cell experiments with in vitro experiments,we determined that the driving force of phase separation of GATA3 is the sharp local concentration difference of GATA3 molecules in cells,and then the driving force of limiting molecular composition and controlling reaction rate in space without membrane chamber.In addition,different morphological characteristics of GATA3-WT,GATA3-?C,GATA3-1-300 and GATA3-1-330 during phase separation would mean different regulatory capacity.Finally,RT q PCR experiment was used to confirm that different mutants of GATA3 have different degrees of regulation ability for downstream target genes.In conclusion,our results preliminarily revealed that GATA3 and its mutants regulate the expression level of downstream target genes through their different molecular characteristics,suggesting that different mutants of GATA3 have different influences on the occurrence and development of breast cancer.This study has a certain basic significance for revealing the detailed pathological mechanism of breast cancer,and provides a way for the follow-up targeted research on the treatment of breast cancer.