Title:ERK/MAPK Signalling Pathway Regulates MMP2 through ETS1 in
Renal Clear Cell Carcinoma
Volume: 24
Issue: 6
Author(s): Hai-Bin Chen, Wei Li*, Zhan Yang*, Kai-Long Liu, Bao-Sai Lu and Zi-Yi Wang
Affiliation:
- Department of Urology, the Second Hospital of Hebei Medical University, Shijiazhuang, 050061, China
- Department of Urology, the Second Hospital of Hebei Medical University, Shijiazhuang, 050061, China
Keywords:
Renal clear cell carcinoma, ETS1, pERK, MMP2, cell proliferation, migration.
Abstract:
Background: The c-ETS-1 (ETS1) expression is high in clear cell renal cell
carcinoma (ccRCC) tissues; however, how it impacts ccRCC is currently unknown.
Methods: The online STRING web source was used to construct a protein network
interacting with ETS1. The Cell Counting Kit-8 was used to detect the cell viability. A
clonogenic assay, a wound-healing assay, and a Transwell assay were used to detect
cell proliferation, invasion and migration abilities. Western blot was used to detect the
expression of proteins.
Results: The data showed the expression of ETS1 in ccRCC tissues to be significantly
increased compared to adjacent tissues (p<0.05). The positive expression of ETS1 in
ccRCC patients aged 20–100 was statistically significant compared to adjacent normal
tissues (p<0.05). The grade of ETS1 positive expression (1-4) and lymph node
metastasis (N1) in ccRCC were significantly higher than those in adjacent normal tissues
(p<0.05). The tumour stage (stages 1-4) in ccRCC patients with positive ETS1 expression
was significantly higher than that in adjacent normal tissues (p<0.05). Knockdown
of ETS1 and PERK inhibitors significantly inhibited the proliferation, migration and
invasion of ccRCC cells. Knockdown of ETS1 inhibited MMP-2 expression, and an
extracellular signal-related kinase (ERK) inhibitor inhibited both ETS1 and MMP-2
expression.
Conclusion: A high expression of ETS1 is associated with the progression of ccRCC.
This study suggests that ETS1 promotes proliferation by increasing MMP2 expression in
ccRCC, and combined knockdown of ETS1 and inhibition of ERK can significantly inhibit
the proliferation, migration and invasion of ccRCC. ETS1 may be a therapeutic and
prognostic target for renal cell carcinoma.
