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Gene & Protein in Disease The roles and mechanisms of ETS1 in diseases

a key molecular switch for EndMT to target the onset of the potential invasion of cancer cells by directing the
MS . overexpression of matrix metalloproteinases (MMPs).
[33]
Nazir et al. demonstrated that the transfection of breast
4. Effect and mechanisms of ETS1 in cancers cancer cell lines with ETS1 siRNA resulted in notable
4.1. Expression of ETS1 in cancers decreases in both ETS1 and MMP-9. In addition, the
knockdown of ETS1 not only attenuated the invasive
Current research shows that ETS1 is highly expressed in potential of cancer cells but also induced alterations in the
various types of cancer cells, such as colorectal cancer, expression of epithelial-mesenchymal transition (EMT)
breast cancer, and endometrial cancer cells, and is related markers .
[42]
to poor differentiation, high potential invasion, high
angiogenesis activity, and increased risk of lymph node The correlation between ETS1 and MMP synthesis has
transition . However, the specific molecular mechanism also been confirmed in a range of cancer types, including
[9]
by which ETS1 operates in the context of cancer remains pancreatic cancer, colon cancer prostate cancer, and
unclear, pending further in-depth exploration and ovarian cancer cells. Multiple signals converge into ETS1 to
comprehensive elucidation. increase the production of MMP. Within pancreatic cancer
cells, the presence of prostaglandin E2 triggers ETS1-driven
Several investigations have shown that ETS1 promotes upregulation of MMP2 expression . In colon cancer cells,
[43]
the development of breast cancer, although the molecular the activation of β6 integrin enhances the ETS1-mediated
mechanism underlying this finding remains obscure [34-36] . expression of both MMP3 and MMP9 . In ovarian cancer
[44]
In addition, a recent study indicated that inducing cells, glycogen synthase kinase-3β (GSK3β) mediates ETS1
ferroptosis in breast cancer through ETS1 degradation phosphorylation, promotes the progression of ovarian
facilitates the promotion of the ETS1-SYVN1 interaction cancer, induces transcriptional activation of MMP9,
by sculponeatin A . Breast cancer cells can promote and increases cell migration. GSK3β inhibitors have
[37]
endothelial cell morphogenesis in a paracrine manner been demonstrated in vivo to inhibit endogenous ETS1
and physically connect with endothelial cells since ETS1 expression and induce MMP9 expression .
[45]
[38]
is a critical regulator of their angiogenic potential .
Furthermore, differential regulation of ETS1 isoforms 4.3. ETS1 and phosphorylation in cancers
(fl-ETS1 and DeltaVII-ETS1) can affect lymphoid The Ras/Raf/MEK/ERK1/2 pathway plays a crucial role in
maturation and homeostasis, and these isoforms exhibit [46]
significant differences in DNA binding, transcriptional modulating ETS1 activity at the posttranslational level .
target specificity, and protein-protein interactions . In The activation of these pathways can lead to N-terminal
[8]
cancer, the balance between fl-ETS1 and DeltaVII-ETS1 phosphorylation of the ETS1 protein at threonine 38 and
[47]
is disrupted. For example, it has been found that a big super activation of ETS1 . The expression of ETS1 in
majority of MDA-MB-231 breast cancer cells have a high the biopsy samples of human breast cancer is correlated
expression of fl-ETS1, and only 10% of these cells exhibit with the level of phosphorylated Raf, suggesting that the
concomitant expression of DeltaVII-ETS1 . However, over activation of ETS1 contributes to the progression of
[39]
[48]
in some cases, the high expression of ETS1 may have an breast cancer . This association underscores the potential
inhibitory effect on breast cancer. Furlan et al. revealed that significance of ETS1 in the context of breast cancer
ETS1 not only promotes malignant tumors by endowing pathogenesis.
them with invasive features but also weakens the growth of The poor prognosis of human ovarian cancer is
breast tumor cells, thus presenting contrasting capabilities possibly accounted for by the enhanced expression of
to promote metastasis and to inhibit the growth of primary ETS1. Tomar et al. made a significant discovery that ETS1
tumors . Recently, Kim et al. reported that ETS1 not only acts as a vital transcription factor triggered in ovarian
[40]
directly activates downstream targets related to tumor cancer cells by the surrounding microenvironment and
cell proliferation and growth, but also activates additional facilitates metastatic colonization by orchestrating the
tumor suppressor genes, such as ADAMTS9, TXNIP, transcriptional upregulation of its target FAK . The
[49]
STAT5A, and NOTCH1, through transactivation . serotonin-rich region (SRR) in ETS1 can automatically
[41]
inhibit its ability to bind DNA. The ability of SRR to inhibit
4.2. ETS1 and matrix metalloproteinases in cancer inflammation has been found to be significantly improved
The specific way in which the highly expressed ETS1 gene by phosphorylation . However, the molecular processes
[50]
promotes the development of cancer cells has not been that control the regulation of ETS1 structure and activity
elucidated, but a large number of studies have shown by phosphorylation remain to be elucidated. Nevertheless,
that ETS1, along with other ETS proteins, facilitates a study by Ning et al. has elucidated the reasons for the

Volume 2 Issue 4 (2023) 4 https://doi.org/10.36922/gpd.2141