Chloride intracellular channel 1 regulates migration and invasion in gastric cancer by triggering the ROS-mediated p38 MAPK signaling pathway

Zhao, Wei; Lu, Mingshu; Zhang, Qiwen

doi:10.3892/mmr.2015.4459

Cited by 39 publications

(23 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In previous studies, the overexpression of c‐myc was positively related to high proliferation activity, and the overexpression and gene amplifications of Myc family members were found in brain tumors . A previous study confirmed that the p38 mitogen‐activated protein kinase (MAPK) signaling pathway was associated with the cellular processes of cell migration and invasion of gastric cancer, and the inhibition of this signaling pathway could potentially result in the restraining of cell migration and invasion . From the aforementioned findings and studies, it was indicated both the p38 MAPK signaling pathway as well as miR‐494 made a great difference in tumor progression.…”

Section: Introductionmentioning

confidence: 90%

Retracted: Effects of microRNA‐494 on proliferation, migration, invasion, and apoptosis of medulloblastoma cells by mediating c‐myc through the p38 MAPK signaling pathway

Zhang

et al. 2018

J of Cellular Biochemistry

View full text Add to dashboard Cite

Medulloblastoma (MB) is the most prevalent brain tumor that occurs during childhood and originates from cerebellar granule cell precursors. Based on recent studies, the differential expression of several microRNAs is involved in MB, while the role of microRNA‐494 (miR‐494) in MB remains unclear. Therefore, we conducted this study to investigate the regulative role of miR‐494 in MB cells via the p38 mitogen‐activated protein kinase (MAPK) signaling pathway by mediating c‐myc. In the current study, MB cells were collected and transfected with miR‐494 mimic, miR‐494 inhibitor, siRNA‐ c‐myc, and miR‐494 inhibitor + siRNA‐c‐myc. The expressions of miR‐494, c‐myc, p38 MAPK, B‐cell lymphoma‐2 (Bcl‐2), Bcl‐2‐associated X protein (Bax), interleukin‐6 (IL‐6), metadherin (MTDH), phosphatase and tensin homolog (PTEN) and survivin were determined. Cell proliferation, cell‐cycle distribution, apoptosis, migration, and invasion were evaluated. The results revealed that there was a poor expression of miR‐494 and high expression of c‐myc in MB tissues. C‐myc was determined as the target gene of miR‐494. In response to miR‐494 mimic, MB cells were found to have increased Bax and PTEN expressions, as well as cell number in G1 phase and cell apoptosis and decreased c‐myc, p38 MAPK, Bcl‐2, MTDH, IL‐6, and survivin expression and cell number count in the S phase, cell proliferation, migration, and invasion. In conclusion, the results demonstrated that the upregulation of miR‐494 results in the suppression of cell proliferation, migration, and invasion, while it promotes apoptosis of MB cells through the negative mediation of c‐myc, which in turn inactivates the p38 MAPK pathway.

show abstract

Section: Introductionmentioning

confidence: 90%

Retracted: Effects of microRNA‐494 on proliferation, migration, invasion, and apoptosis of medulloblastoma cells by mediating c‐myc through the p38 MAPK signaling pathway

Zhang

et al. 2018

J of Cellular Biochemistry

View full text Add to dashboard Cite

show abstract

“…Viral proteins modulate cellular ion channel functionality to favor their life cycles ( 2 ). In recent years, Cl − channels have emerged as some of the most active cellular ion channels during tumorigenesis, because of their involvement in both cell motility and proliferation ( 17 , 18 ). We reasoned that Cl − channels could therefore play a role in MCPyV ST-induced cell motility.…”

Section: Resultsmentioning

confidence: 99%

“…A key question remains, how does MCPyV ST target CLIC1 and CLIC4, and how does this ultimately benefit the virus? Both channels are widely expressed and their activity regulates components of the cytoskeleton, adhesion molecules, and cell signaling pathways ( 18 , 27 , 30 ), all of which may contribute to MCPyV ST tumor formation. We observed that the MCPyV ST effects on CLIC1/CLIC4 did not occur at the transcriptional level, ruling out the involvement of known MCPyV ST cellular targets including p53 and tumor necrosis factor α (TNFα) ( 31 – 33 ) that regulate CLIC transcript levels.…”

Section: Discussionmentioning

confidence: 99%

The cellular chloride channels CLIC1 and CLIC4 contribute to virus-mediated cell motility

Stakaitytė

Nwogu

Lippiat

et al. 2018

Journal of Biological Chemistry

View full text Add to dashboard Cite

Ion channels regulate many aspects of cell physiology, including cell proliferation, motility, and migration, and aberrant expression and activity of ion channels is associated with various stages of tumor development, with K+ and Cl− channels now being considered the most active during tumorigenesis. Accordingly, emerging in vitro and preclinical studies have revealed that pharmacological manipulation of ion channel activity offers protection against several cancers. Merkel cell polyomavirus (MCPyV) is a major cause of Merkel cell carcinoma (MCC), primarily because of the expression of two early regulatory proteins termed small and large tumor antigens (ST and LT, respectively). Several molecular mechanisms have been attributed to MCPyV-mediated cancer formation but, thus far, no studies have investigated any potential link to cellular ion channels. Here we demonstrate that Cl− channel modulation can reduce MCPyV ST-induced cell motility and invasiveness. Proteomic analysis revealed that MCPyV ST up-regulates two Cl− channels, CLIC1 and CLIC4, which when silenced, inhibit MCPyV ST-induced motility and invasiveness, implicating their function as critical to MCPyV-induced metastatic processes. Consistent with these data, we confirmed that CLIC1 and CLIC4 are up-regulated in primary MCPyV-positive MCC patient samples. We therefore, for the first time, implicate cellular ion channels as a key host cell factor contributing to virus-mediated cellular transformation. Given the intense interest in ion channel modulating drugs for human disease. This highlights CLIC1 and CLIC4 activity as potential targets for MCPyV-induced MCC.

show abstract

“…At low or endurable levels, ROS may aid cancer progression either by playing as signaling elements or by stimulating alterations in genomic DNA or DNA damage. For example, ROS can promote expression of cyclin D1, phosphorylation of extracellular signal-regulated kinase (ERK) and JUN N-terminal kinase (JNK), and activation of mitogen-activated protein kinase (MAPK), all of which are connected to cancer progression and survival [ 260 , 261 , 262 , 263 , 264 , 265 ]. Moreover, ROS have been found to inversely incapacitate tumor suppressors, including protein tyrosine phosphatases (PTPs) and phosphatase and tensin homolog (PTEN), due to the existence of the redox-sensitive cysteine residues that exist in their catalytic sites [ 266 , 267 , 268 ].…”

Section: The Association Between Oxidative Stress and Cancer Progrmentioning

confidence: 99%

Correlation between Oxidative Stress, Nutrition, and Cancer Initiation

Saha

Lee

Won

et al. 2017

IJMS

332

205

View full text Add to dashboard Cite

Inadequate or excessive nutrient consumption leads to oxidative stress, which may disrupt oxidative homeostasis, activate a cascade of molecular pathways, and alter the metabolic status of various tissues. Several foods and consumption patterns have been associated with various cancers and approximately 30–35% of the cancer cases are correlated with overnutrition or malnutrition. However, several contradictory studies are available regarding the association between diet and cancer risk, which remains to be elucidated. Concurrently, oxidative stress is a crucial factor for cancer progression and therapy. Nutritional oxidative stress may be induced by an imbalance between antioxidant defense and pro-oxidant load due to inadequate or excess nutrient supply. Oxidative stress is a physiological state where high levels of reactive oxygen species (ROS) and free radicals are generated. Several signaling pathways associated with carcinogenesis can additionally control ROS generation and regulate ROS downstream mechanisms, which could have potential implications in anticancer research. Cancer initiation may be modulated by the nutrition-mediated elevation in ROS levels, which can stimulate cancer initiation by triggering DNA mutations, damage, and pro-oncogenic signaling. Therefore, in this review, we have provided an overview of the relationship between nutrition, oxidative stress, and cancer initiation, and evaluated the impact of nutrient-mediated regulation of antioxidant capability against cancer therapy.

show abstract

Chloride intracellular channel 1 regulates migration and invasion in gastric cancer by triggering the ROS-mediated p38 MAPK signaling pathway

Cited by 39 publications

References 39 publications

Retracted: Effects of microRNA‐494 on proliferation, migration, invasion, and apoptosis of medulloblastoma cells by mediating c‐myc through the p38 MAPK signaling pathway

Retracted: Effects of microRNA‐494 on proliferation, migration, invasion, and apoptosis of medulloblastoma cells by mediating c‐myc through the p38 MAPK signaling pathway

The cellular chloride channels CLIC1 and CLIC4 contribute to virus-mediated cell motility

Correlation between Oxidative Stress, Nutrition, and Cancer Initiation

Contact Info

Product

Resources

About