scholarly journals Galectin-8 binds to the Farnesylated C-terminus of K-Ras4B and Modifies Ras/ERK Signaling and Migration in Pancreatic and Lung Carcinoma Cells

Cancers ◽  
2019 ◽  
Vol 12 (1) ◽  
pp. 30 ◽  
Author(s):  
Christopher Meinohl ◽  
Sarah J. Barnard ◽  
Karin Fritz-Wolf ◽  
Monika Unger ◽  
Andreea Porr ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Pancreatic Carcinoma ◽  
Binding Pocket ◽  
Carcinoma Cells ◽  
Binding Assays ◽  
Lung Carcinoma Cells ◽  
C Terminus ◽  
Carbohydrate Recognition Domains ◽  
And Migration ◽  
Effector Pathways

K-Ras is the most prominent driver of oncogenesis and no effective K-Ras inhibitors have been established despite decades of intensive research. Identifying new K-Ras-binding proteins and their interaction domains offers the opportunity for defining new approaches in tackling oncogenic K-Ras. We have identified Galectin-8 as a novel, direct binding protein for K-Ras4B by mass spectrometry analyses and protein interaction studies. Galectin-8 is a tandem-repeat Galectin and it is widely expressed in lung and pancreatic carcinoma cells. siRNA-mediated depletion of Galectin-8 resulted in increased K-Ras4B content and ERK1/2 activity in lung and pancreatic carcinoma cells. Moreover, cell migration and cell proliferation were inhibited by the depletion of Galectin-8. The K-Ras4B–Galectin-8 interaction is indispensably associated with the farnesylation of K-Ras4B. The lysine-rich polybasic domain (PBD), a region that is unique for K-Ras4B as compared to H- and N-Ras, stabilizes the interaction and accounts for the specificity. Binding assays with the deletion mutants of Galectin-8, comprising either of the two carbohydrate recognition domains (CRD), revealed that K-Ras4B only interacts with the N-CRD, but not with the C-CRD. Structural modeling uncovers a potential binding pocket for the hydrophobic farnesyl chain of K-Ras4B and a cluster of negatively charged amino acids for interaction with the positively charged lysine residues in the N-CRD. Our results demonstrate that Galectin-8 is a new binding partner for K-Ras4B and it interacts via the N-CRD with the farnesylated PBD of K-Ras, thereby modulating the K-Ras effector pathways as well as cell proliferation and migration.

scholarly journals CIP2A, an oncoprotein, is associated with cell proliferation, invasion and migration in laryngeal carcinoma cells

2017 ◽  
Vol 38 (2) ◽  
pp. 1005-1012 ◽  
Author(s):  
Xu-Dong Chen ◽  
Shi-Xiong Tang ◽  
Jian-Hua Zhang ◽  
Li-Tao Zhang ◽  
Yao-Wen Wang
Keyword(s):  
Cell Proliferation ◽  
Laryngeal Carcinoma ◽  
Carcinoma Cells ◽  
Invasion And Migration ◽  
And Migration

Effect of fasudil on growth, adhesion, invasion, and migration of 95D lung carcinoma cells in vitro

2010 ◽  
Vol 88 (9) ◽  
pp. 874-879 ◽  
Author(s):  
Xueying Yang ◽  
Yang Zhang ◽  
Shumin Wang ◽  
Wenjun Shi
Keyword(s):  
Lung Carcinoma ◽  
Molecular Mechanisms ◽  
Kinase Inhibitor ◽  
Rho Kinase ◽  
Carcinoma Cells ◽  
Migration And Invasion ◽  
Invasion And Migration ◽  
Lung Carcinoma Cells ◽  
Rho Kinase Inhibitor ◽  
And Migration

The objective of the study was to investigate the effects of a Rho-kinase inhibitor on 95D lung carcinoma cell growth, adhesion, invasion, and migration and to explore the underlying molecular mechanisms involved in this process. After treatment of 95D lung carcinoma cells with fasudil, an inhibitor of Rho-kinase, cell biological behaviors such as growth, adhesion, invasion, and migration were observed. Matrix metalloproteinase (MMP) activity and Western blot assay were used to evaluate underlying molecular mechanisms. The IC50 of fasudil to 95D lung carcinoma cells was approximately 0.79 mg/mL (95% confidence limits 0.58–1.11 mg/mL). After treatment with 0.75 mg/mL fasudil, the ability of 95D lung carcinoma cells for growth, adhesion, migration, and invasion was decreased significantly. Total active MMP2 was decreased approximately 22.7% (p < 0.05) and total MMP9 65.9% (p < 0.01). Myosin phosphatase target subunit 1 (MYPT1) was reduced by 29.4% (p < 0.05). We conclude that the Rho-kinase inhibitor prevents the growth, adhesion, invasion, and migration of 95D lung carcinoma cells by inhibiting the Rho/Rho-kinase pathway. Changes in MMP2, MMP9, and MYPT1 may be part of its molecular mechanisms.

scholarly journals LncRNA MALAT1 Regulating Lung Carcinoma Progression via the miR-491-5p/UBE2C Axis

2021 ◽  
Vol 27 ◽  
Author(s):  
Juanjuan Dai ◽  
Ning Zhou ◽  
Rui Wu ◽  
Jing Du ◽  
Shuang Miao ◽  
...  
Keyword(s):  
Lung Carcinoma ◽  
Critical Role ◽  
Carcinoma Cells ◽  
Migration Ability ◽  
Invasion And Migration ◽  
Lung Carcinoma Cells ◽  
Lncrna Malat1 ◽  
Anti Cancer ◽  
And Migration

Long noncoding RNAs (lncRNAs) play a critical role in the development of lung carcinoma. The mechanism of MALAT1 in lung carcinoma development is not understood very well. This study aimed to investigate the role of MALAT1 in lung carcinoma progression and the mechanism underlying the role of miR-491-5p in the MALAT1 mediated regulation of UBE2C expression. The results indicated that the expression of MALAT1 was often augmented in lung carcinoma cells. Suppression of MALAT1 blocked the proliferation, invasion and migration ability of cancer cells and inhibited the expression of UBE2C. UBE2C restoration attenuated the MALAT1 knockdown-induced anti-cancer effects. Moreover, UBE2C and MALAT1 were indicated as targets of miR-491-5p and inhibition of miR-491-5p restored the MALAT1 knockdown-induced inhibition of the progression of lung carcinoma. Furthermore, MALAT1 sponged miR-491-5p to upregulate UBE2C expression, causing it to act as a competing endogenous RNA. Collectively, MALAT1 downregulation suppressed lung carcinoma progression by regulating the miR-491-5p/UBE2C axis. These results indicate that MALAT1 could be a molecular target for lung carcinoma treatment and prognosis.

scholarly journals Solanine Attenuated Hepatocarcinoma Migration and Invasion Induced by Acetylcholine

2020 ◽  
Vol 19 ◽  
pp. 153473542090989
Author(s):  
Liang-Tzung Lin ◽  
Chen-Yen Choong ◽  
Chen-Jei Tai
Keyword(s):  
Cell Proliferation ◽  
Carcinoma Cells ◽  
Migration And Invasion ◽  
Hep G2 ◽  
Hep G2 Cells ◽  
Mesenchymal Transition ◽  
Cell Proliferation And Migration ◽  
G2 Cells ◽  
And Migration ◽  
Proliferation And Migration

Aim: Evidence has provided an explanation of the correlation between the nervous system and the tumor microenvironment. Neurotransmitters may be involved in different aspects of cancer progression. The glycoalkaloid solanine has been reported to suppress neural signaling pathways and exists in numerous plants, including Solanum nigrum, which have been demonstrated to inhibit cancer cell proliferation. Methods: We evaluated the potentials of solanine on inhibiting acetylcholine-induced cell proliferation and migration in hepatocellular carcinoma cells. Results: The results indicated that solanine markedly attenuated cell proliferation and migration via inhibiting epithelial-mesenchymal transition and matrix metalloproteinases in acetylcholine-treated Hep G2 cells. In addition, exosomes derived from acetylcholine-treated Hep G2 cells were isolated, and solanine showed inhibiting effects of extrahepatic metastasis on blocking cell proliferation in exosome-treated A549 lung carcinoma cells through regulating microRNA-21 expression. Conclusion: Solanine has strong potential for application in integrative cancer therapy.

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