143: Zoledronate suppresses human osteosarcoma (U2OS) cells invasion and migration by affecting cell morphology and cytoskeletal organization via FAK, RhoA, Ras, vimentin and E-cadherin

2014 ◽  
Vol 50 ◽  
pp. S32
Author(s):  
K. Lu ◽  
S. Yang
Molecules ◽  
2020 ◽  
Vol 25 (2) ◽  
pp. 326 ◽  
Author(s):  
Min-Hong Hsieh ◽  
Jia-Sin Yang ◽  
Renn-Chia Lin ◽  
Yi-Hsien Hsieh ◽  
Shun-Fa Yang ◽  
...  

Osteosarcoma, which is the most prevalent malignant bone tumor, is responsible for the great majority of bone cancer-associated deaths because of its highly metastatic potential. Although tomatidine is suggested to serve as a chemosensitizer in multidrug-resistant tumors, the anti-metastatic effect of tomatidine in osteosarcoma is still unknown. Here, we tested the hypothesis that tomatidine suppresses migration and invasion, features that are associated with metastatic process in human osteosarcoma cells and also investigate its underlying pathway. Tomatidine, up to 100 μM, without cytotoxicity, inhibited the invasion and migration capabilities of human osteosarcoma U2OS and HOS cells and repressed presenilin 1 (PS-1) expression of U2OS cells. After the knockdown of PS-1, U2OS and HOS cells’ biological behaviors of cellular invasion and migratory potential were significantly reduced. While tomatidine significantly decreased the phosphorylation of c-Raf, mitogen/extracellular signal-regulated kinase (MEK), and extracellular signal-regulated protein kinase (ERK)1/2 in U2OS cells, no obvious influences on p-Jun N-terminal kinase, p38, and Akt, including their phosphorylation, were observed. In ERK 1 silencing U2 OS cells, tomatidine further enhanced the decrease of their migratory potential and invasive activities. We conclude that both PS-1 derived from U2OS and HOS cells and the c-Raf–MEK–ERK pathway contribute to cellular invasion and migration and tomatidine could inhibit the phenomenons. These findings indicate that tomatidine might be a potential candidate for anti-metastasis treatment of human osteosarcoma.


2021 ◽  
Author(s):  
Wei Mai ◽  
Lingyu Kong ◽  
Hongwei Yu ◽  
Junjie Bao ◽  
Chunyu Song ◽  
...  

Aim: Typical features of human osteosarcoma are highly invasive and migratory capacities. Our study aimed to investigate the roles of glycogen synthase kinase 3β (GSK3β) in human osteosarcoma metastasis. Methods: GSK3β expressions in clinical osteosarcoma tissues with or without metastasis were examined by immunohistochemical staining. The expressions of GSK3β, p-GSK3βSer9, and p-GSK3βTyr216 in human osteoblast cells (hFOB1.19) and human osteosarcoma cells (MG63, SaOS-2 and U2-OS) were detected by western blotting. The GSK3β activity was measured by non-radio isotopic in vitro kinase assay. Migration and invasion abilities of MG-63 cells treated with small-molecular GSK3β inhibitors were respectively examined by monolayer-based wound-healing assay and transwell assay. The mRNA expressions of GSK3β, matrix metalloproteinase-2 (MMP-2), MMP-9, phosphatase with tensin homology (PTEN), and focal adhesion kinase (FAK) were detected after siRNA transfection for 72 h. Meanwhile, protein expressions of GSK3β, FAK, p-FAKY397, PTEN, MMP-2, and MMP-9 were measured by western blotting. Results: Clinical osteosarcoma tissues with metastasis showed higher GSK3β expressions. MG63 and U2-OS cells which were easy to occur metastasis showed significantly higher expressions and activities of GSK3β than SaOS-2 cells. Inhibition of GSK3β with small-molecular GSK3β inhibitors in MG63 cells significantly attenuated cell migration and invasion. These effects were associated with reduced expressions of MMP-2 and MMP-9. Moreover, increased PTEN and decreased p-FAKY397 expressions were observed following GSK3b knock-down by siRNA transfection. Conclusion: GSK3β might promote osteosarcoma invasion and migration via pathways associated with PTEN and phosphorylation of FAK.


Placenta ◽  
2020 ◽  
Vol 97 ◽  
pp. 18-25
Author(s):  
Hailing Zhu ◽  
Xia Niu ◽  
Qinghua Li ◽  
Yuehua Zhao ◽  
Xue Chen ◽  
...  

2019 ◽  
Vol 9 (9) ◽  
pp. 1215-1221
Author(s):  
Li Jie ◽  
Zhangcai Zheng ◽  
Liping Liu ◽  
Yali Liu ◽  
Zhaoyan Meng ◽  
...  

Preeclampsia (PE) is an idiopathic hypertension syndrome occurring after 20 weeks of gestation. Reports showed that lncRNAs expression was abnormal in preeclampsia. We aimed to investigate the role of lncRNA CEACAMP8 in the proliferation, invasion and migration of trophoblast cells to improve the preeclampsia. The cell transfection effects were determined by RT-qPCR analysis. The proliferation, invasion and migration of HTR-8/SVneo cells were detected by CCK-8 assay, transwell assay and wound healing assay. The flow cytometry analysis analyzed the cell cycle. Moreover, the expression of CDK2, cyclinD1, P21, MMP2, MMP9, E-cadherin, b-catenin and vimentin was determined by the western blot analysis. Consequently, CEACAMP8 inhibition promoted the proliferation, invasion and migration of HTR-8/SVneo cells and kept most of the cells in the S phase. The expression of proteins related to the proliferation, invasion and migration of HTR-8/SVneo cells were also changed in accordance with the increase of proliferation, invasion and migration of HTR-8/SVneo cells. In addition, lncRNA CEACAMP8 inhibition decreased the expression of E-cadherin and b-catenin, and increased the vimentin expression to promote the epithelial-mesenchymal transition. And, CEACAMP8 overexpression could reverse the above changes. This study indicated that CEACAMP8 inhibition promoted the proliferation, invasion and migration of HTR-8/SVneo cells and lncRNA CEACAMP8 overexpression reversed.


Tumor Biology ◽  
2017 ◽  
Vol 39 (5) ◽  
pp. 101042831770533 ◽  
Author(s):  
Lin Liu ◽  
Long Miao ◽  
Yang Liu ◽  
Aihua Qi ◽  
Ping Xie ◽  
...  

S100A11 is a S100 protein family member that contributes to cancer progression. Upregulated in human renal cancer tissues, S100A11 may be a prognostic marker for clear cell renal cell carcinoma, but how it functions in cancer is uncertain. Thus, we studied S100A11 and noted knockdown of S100A11 using short hairpin RNA, which inhibited proliferation, invasion, and migration of renal carcinoma cells as well as increased expression of E-cadherin and decreased expression of epidermal growth factor receptor/Akt in renal carcinoma cells. Therefore, S100A11 may be a key molecular target for treating renal carcinoma.


Author(s):  
Akihiro Murakami ◽  
Tatsushi Nakagawa ◽  
Mayumi Kaneko ◽  
Shugo Nawata ◽  
Osamu Takeda ◽  
...  

2021 ◽  
Vol 11 (3) ◽  
pp. 426-432
Author(s):  
Xiancheng Kong ◽  
Hao Zhang ◽  
Jianping Huang ◽  
Liang Yan ◽  
Li Sha ◽  
...  

Colon cancer is a common malignancy of the digestive tract, mostly occurring at the junction of the rectum and colon. It easily invades multiple internal organs and tissues, causing systemic injury and mortality to patients. The occurrence and development of colon cancer involve multiple genes and multiple factors. It is greatly significant to identify oncogenes and tumor suppressor genes that influence the development of colon cancer and to study their mechanism of action for colon cancer diagnosis and treatment. Furthermore, circRNA are involved in the development of several types of tumors by affecting miRNA regulation on target gene expression. In the present study, circ_0005075 siRNA and circ_0005075 siRNA + mir-335 inhibitor were transfected into colon cancer SW620 cells, and circ_0005075 gene expression was significantly decreased after transfecting circ_0005075 siRNA into SW620 cells. Silencing circ_0005075 expression significantly inhibited SW620 cell proliferation, invasion, and migration, and promoted apoptosis, downregulated PCNA and vimentin expression, and upregulated E-cadherin and cleaved caspase3 expression. After circ_0005075 siRNA + mir-335 was transfected, it inhibited circ_0005075 and mir-335 expression, which significantly affected the vigor, invasion and migration ability, apoptosis rate of SW620 cells, as well as PCNA, E-cadherin, vimentin, and cleaved caspase3 expression. Therefore, the present study demonstrated that circ_0005075 silencing inhibited the proliferation, invasion, and migration of SW620 cells and promoted apoptosis by upregulating mir-335 expression.


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