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Abstract
Aggressive and mesenchymal-transformed breast cancer cells show high expression levels of Rho GTPase activating protein 29 (ARHGAP29), a negative regulator of RhoA. ARHGAP29 was the only one of 32 GTPase-activating enzymes whose expression significantly increased after the induction of mesenchymal transformation in breast cancer cells. Therefore, we investigated the influence of ARHGAP29 on the invasiveness of aggressive and mesenchymal-transformed breast cancer cells. After knock-down of ARHGAP29 using siRNA, invasion of HCC1806, MCF-7-EMT, and T-47D-EMT breast cancer cells was significantly reduced. This could be explained by reduced inhibition of RhoA and a consequent increase in stress fiber formation. Proliferation of the breast cancer cell line T-47D-EMT was slightly increased by reduced expression of ARHGAP29, whereas that of HCC1806 and MCF-7-EMT significantly increased. Using interaction analyses we found that AKT1 is a possible interaction partner of ARHGAP29. Therefore, the expression of AKT1 after siRNA knock-down of ARHGAP29 was tested. Reduced ARHGAP29 expression was accompanied by significantly reduced AKT1 expression. However, the ratio of active pAKT1 to total AKT1 remained unchanged or was significantly increased after ARHGAP29 knock-down. Our results show that ARHGAP29 could be an important factor in the invasion of aggressive and mesenchymal-transformed breast cancer cells. Further research is required to fully understand the underlying mechanisms.
Highlights
With almost 2.1 million new diagnoses (11.6% of incidence) and 627,000 deaths (6.6% of mortality) in 2018, breast cancer is the world’s second most common cancer and the most common cancer experienced by women [1,2]
MCF-7-epithelial–mesenchymal transition (EMT) breast cancer cells showed that 223 genes were upregulated by the induction of EMT
Rho GTPase activating protein 29 (ARHGAP29) has a suppressive effect with higher specificity for RhoA compared with Rac and CDC42 [6,9,12]
Summary
With almost 2.1 million new diagnoses (11.6% of incidence) and 627,000 deaths (6.6% of mortality) in 2018, breast cancer is the world’s second most common cancer and the most common cancer experienced by women [1,2]. Due to early detection and improved therapeutic options, 5-year survival rates for local and regional breast cancers are 84–99%. Only 27% of patients diagnosed with distant metastases survive a period of five years [3]. Epithelial-mesenchymal transition (EMT) is a dynamic, temporary, and plastic process that goes hand-in-hand with a change from immobile, polarized epithelial cells to mobile, invasive mesenchymal cells [5]. By going through this process, there is a loss of cell–cell adhesion and cell polarity and an increase in mesenchymal properties
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