High activation of DNA damage response is implicated in cisplatin (CDDP) resistance which presents as a serious obstacle for bladder cancer treatment. Cdc6 plays an important role in the malignant progression of tumor. Here, we reported that Cdc6 expression is up-regulated in bladder cancer tissues and is positively correlated to high tumor grade. Cdc6 depletion can attenuate the malignant properties of bladder cancer cells, including DNA replication, migration and invasion. Furthermore, higher levels of chromatin-binding Cdc6 and ATR were detected in CDDP-resistant bladder cancer cells than in the parent bladder cancer cells. Intriguingly, down-regulation of Cdc6 can enhance sensitivity to CDDP both in bladder cancer cells and CDDP-resistant bladder cancer cells. Cdc6 depletion abrogates S phase arrest caused by CDDP, leading to aberrant mitosis by inactivating ATR-Chk1-Cdc25C pathway. Our results indicate that Cdc6 may be a promising target for overcoming CDDP resistance in bladder cancer.
Special AT-rich sequence-binding protein-1 (SATB1) is associated with cancer progression and poor clinical outcome. The present study aims to evaluate whether SATB1 affects the biological behaviors of prostate cancer (PCa), and furthermore, to elucidate whether this effect works through the epithelial-mesenchymal transition (EMT) pathway. Firstly, the expression of SATB1 was investigated in a series of PCa tissues as well as in a panel of PCa cell lines. Cell proliferation, migration and invasion were evaluated in SATB1 knockdown and overexpressed PCa cell lines by MTT and Transwell assays. The results showed that the expression of SATB1 was markedly upregulated in PCa tissues and all PCa cell lines (P<0.001). Ectopic expression of SATB1 promoted PCa cell proliferation and migration. Knockdown of SATB1 repressed the ability of cell proliferation and migration of PCa cells. In addition, inhibition of SATB1 could reverse the EMT processes through upregulation of E-cadherin and downregulation of vimentin. The present study provided evidence that SATB1 may act as a potential therapeutic target in PCa patients.
These results suggest that CIP2A is involved in tumor progression, and thus CIP2A could represent selective targets for the targeted treatments of bladder cancer.
Background
Breast cancer (BC), the most common cause of cancer death in women, overtook lung cancer as the leading cause of cancer worldwide in 2020. Although many studies have proposed KIN17 as a biomarker of tumorigenesis in different cancer types, its role in tumor metastasis, particularly in BC metastasis, has been underexplored. This study aimed to explore the role of KIN17 in BC metastasis.
Methods
Survival analyses was performed to identify the association between KIN17 expression and BC patient survival
in silico
. Using lentivirus constructs, we developed bidirectional KIN17 expression (KD, knockdown; OE, overexpression) cellular models of luminal‐A (Lum‐A) breast cancer MCF‐7 cells. We performed
in vitro
wound healing, transwell with and without Matrigel assays, and
in vivo
tail‐vein metastasis assay to evaluate the migration and invasion abilities of MCF‐7 with stable KIN17 knockdown or overexpression. Western blotting was performed to compare the changes in protein expression.
Results
We found that KIN17 expression was associated with poor overall survival (OS), relapse‐free survival (RFS), distant metastasis‐free survival (DMFS) and post‐progression survival (PPS), particularly in Lum‐A breast cancer patients. Later, we found that KIN17 knockdown inhibited migration and invasion of MCF‐7 cells via regulating EMT‐associated signaling pathways in vitro and decreases metastatic spread of the disease
in vivo
. In contrast, KIN17 overexpression promoted migration and invasion of MCF‐7 cells in vitro and increased the metastatic spread of the disease
in vivo
.
Conclusions
Overall, our findings provide preliminary data which suggests KIN17 of importance to target in metastatic Lum‐A patients.
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