RESUMEN
Triple-negative breast cancer (TNBC) poses a serious therapeutic challenge due to the occurrence of frequently aggressive, heterogenic, and metastatic tumours. The absence of therapeutic targets for traditional therapies is a hindrance to establishing a standardised therapy for TNBC. There is limited TNBCs epidemiological and real-world data about TNBC treatment regimens in Poland. We retrospectively analysed clinical data from our hospital registry from 2015 and 2020. A total of 8103 individuals with breast cancer were admitted to the MSCI, while 856 (10.6%) were diagnosed with TNBC. Most of the early-stage or locally advanced TNBC individuals had underlying conditions, presented mostly poorly differentiated (G3) stage II tumours and featured a bi-modal age distribution. On average, one-third of all tested TNBCs carried BRCA mutations and its identification impacted surgery preference. We observed a significant increase in the use of systemic therapy among TNBCs, whereas carboplatin and dose-dense regimens showed the most prominent upsurge in the neoadjuvant setting. Moreover, the use of neoadjuvants was positively correlated with less invasive breast and lymph node surgeries. The presented data align with general trends observed in other countries and will contribute to expanding knowledge in the planning of treatment regimens and their outcomes.
RESUMEN
The Arabidopsis ERECTA family (ERf) of leucine-rich repeat receptor-like kinases (LRR-RLKs) comprising ERECTA (ER), ERECTA-LIKE 1 (ERL1), and ERECTA-LIKE 2 (ERL2) controls epidermal patterning, inflorescence architecture, and stomata development and patterning. These proteins are reported to be plasma membrane associated. Here we show that the er/erl1/erl2 mutant exhibits impaired gibberellin (GA) biosynthesis and perception alongside broad transcriptional changes. The ERf kinase domains were found to localize to the nucleus where they interact with the SWI3B subunit of the SWI/SNF chromatin remodeling complex (CRCs). The er/erl1/erl2 mutant exhibits reduced SWI3B protein level and affected nucleosomal chromatin structure. Similar to swi3c and brm plants with inactivated subunits of SWI/SNF CRCs, it also does not accumulate DELLA RGA and GAI proteins. The ER kinase phosphorylates SWI3B in vitro, and the inactivation of all ERf proteins leads to the decreased phosphorylation of SWI3B protein in vivo. The identified correlation between DELLA overaccumulation and SWI3B proteasomal degradation, and the physical interaction of SWI3B with DELLA proteins indicate an important role of SWI3B-containing SWI/SNF CRCs in gibberellin signaling. Co-localization of ER and SWI3B on GID1 (GIBBERELLIN INSENSITIVE DWARF 1) DELLA target gene promoter regions and abolished SWI3B binding to GID1 promoters in er/erl1/erl2 plants supports the conclusion that ERf-SWI/SNF CRC interaction is important for transcriptional control of GA receptors. Thus, the involvement of ERf proteins in the transcriptional control of gene expression, and observed similar features for human HER2 (epidermal growth family receptor member), indicate an exciting target for further studies of evolutionarily conserved non-canonical functions of eukaryotic membrane receptors.
