Downregulation of NPM expression by Her-2 reduces resistance of gastric cancer to oxaliplatin

Sun, Zhenni; Lu, Yue; Shen, Zan; Li, Yong; Sui, Aihua; Li, Tianjun; Tang, Qian; Yao, Ruyong; Sun, Yongning

doi:10.3892/ol.2017.5722

Cited by 7 publications

(7 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover, NPM1 overexpression also correlates well with recurrence and progression of bladder cancer to advanced stages and is associated with acquired estrogen‐independence in human breast cancer cells . In gastric cancer, NPM1 expression is correlated with resistance to the drug oxaliplatin .…”

Section: Introductionmentioning

confidence: 98%

Oncogene c‐fos and mutant R175H p53 regulate expression of Nucleophosmin implicating cancer manifestation

et al. 2018

View full text Add to dashboard Cite

Nucleophosmin (NPM1) is a nucleolar protein that is frequently overexpressed in various types of solid tumors. NPM1 is involved in several cellular processes that might contribute significantly to the increased proliferation potential of cancers. Previous reports suggest that NPM1 expression is highly increased in response to mitogenic and oncogenic signals, the mechanisms of which have not been elucidated extensively. Using constructs incorporating different fragments of the NPM1 promoter upstream to a Luciferase reporter gene, we have identified the minimal promoter of NPM1 and candidate transcription factors regulating NPM1 promoter activity by luciferase reporter assays. We have validated the roles of a few candidate factors at the transcriptional and protein level by quantitative reverse transcriptase PCR, immunoblotting and immunohistochemistry, and explored the mechanism of regulation of NPM1 expression using immunoprecipitation and chromatin immunoprecipitation assays. We show here that the expression of NPM1 is regulated by transcription factor c-fos, a protein that is strongly activated by growth factor signals. In addition, mutant p53 (R175H) overexpression also enhances NPM1 expression possibly through c-myc and c-fos. Moreover, both c-fos and mutant p53 are overexpressed in oral tumor tissues that showed NPM1 overexpression. Collectively, our results suggest that c-fos and mutant p53 R175H positively regulate NPM1 expression, possibly in synergism, that might lead to oncogenic manifestation.

show abstract

Section: Introductionmentioning

confidence: 98%

Oncogene c‐fos and mutant R175H p53 regulate expression of Nucleophosmin implicating cancer manifestation

et al. 2018

View full text Add to dashboard Cite

show abstract

“…Importantly, the HER2-positive status was associated with a poor prognosis and other relevant clinicopathological characteristics (37). A recent study provides the evidence that the inhibition of HER2 can significantly reverse the drug-resistance of gastric cancer cells (14). Furthermore, a positive relationship between the expression levels of Met and HER2 has been observed.…”

Section: Discussionmentioning

confidence: 98%

“…Human epidermal growth factor receptor-2 (HER2) is abnormally expressed in gastric cancer and is closely associated with cancer chemoresistance. Inhibition of HER2-expression significantly increases the sensitivity of cells to chemotherapeutic drugs (14). A positive crosstalk exists between Met and HER2, and both of them increase the resistance of GC cells to cisplatin (15).…”

Section: Cav-1 Induces the Her2 Expression By Activating Met In Gc Cellsmentioning

confidence: 99%

Caveolin-1 Promotes Chemoresistance of Gastric Cancer Cells to Cisplatin by Activating WNT/β-Catenin Pathway

et al. 2020

View full text Add to dashboard Cite

Drug resistance is a major challenge for chemotherapy in treating human gastric cancer (GC), as the underlying molecular mechanism of chemoresistance in GC remains unknown. Caveolin-1 (Cav-1) is a scaffold protein of plasma membrane caveolae that acts as a tumor modulator by interacting with several cell signals. In this research, we showed that the survival rate of GC cells to cisplatin (CDDP) increased in the presence of Cav-1. Moreover, Cav-1 overexpression inhibited cisplatin-induced apoptosis and improved the survival rate of GC cells. Cav-1 overexpression and knock-down experiments indicated that Cav-1 expression stimulated wingless-type MMTV integration site (WNTs) pathway through the phosphorylation of LRP6 and dephosphorylation of β-catenin. Cav-1 was positively associated with the increase of WNT downstream target gene Met, which led to the activation of HER2 signaling. Moreover, our results demonstrated that the expression of Cav-1 and Met were positively associated with the resistance of GC cells to cisplatin. Collectively, Cav-1 enhances the cisplatin-resistance of GC cells by activating the WNT signaling pathway and Met-HER2 crosstalk. Understanding the role of Cav-1 in the chemoresistance of GC would help to develop novel therapies for a better treatment outcome of GC patients.

show abstract

“…Several molecular mechanisms conferring resistance to OXA have been reported in many types of human cancers . Cancer cells are initially susceptible to chemotherapeutic agents; they can acquire resistance to OXA gradually through diverse mechanisms, such as apoptosis, transcription factors, and DNA repair systems .…”

Section: Introductionmentioning

confidence: 99%

“…Several molecular mechanisms conferring resistance to OXA have been reported in many types of human cancers. [6][7][8] Cancer cells are initially susceptible to chemotherapeutic agents; they can acquire resistance to OXA gradually through diverse mechanisms, such as apoptosis, transcription factors, and DNA repair systems. 9 High-mobility group box 1 (HMGB1), a nuclear chromosomal protein, acts as an extracellular "damage-associated molecular pattern" (DAMP) molecule, which has been detected in several human diseases as well as several cancer types.…”

mentioning

confidence: 99%

Metformin increases the cytotoxicity of oxaliplatin in human DLD‐1 colorectal cancer cells through down‐regulating HMGB1 expression

Huang

Lin

Chen

et al. 2018

J of Cellular Biochemistry

View full text Add to dashboard Cite

Colorectal cancer (CRC) is the fourth most common cause of cancer death worldwide. Chemotherapy has been the major strategy for treating patients with advanced CRC. Oxaliplatin (OXA) is used as both an adjuvant and neoadjuvant anticancer agent available to treat advanced CRC. High-mobility group box 1 protein (HMGB1) is a critical regulator of cell death and survival. HMGB1 overexpression has been shown to be resistant to cytotoxic agents. In addition, Metformin, a widely used drug for diabetes, has emerged as a potential anticancer agent. In this study, we examined whether HMGB1 plays a role in the OXA- and/or metformin-induced cytotoxic effect on CRC cells. The results showed that treatment with OXA increased HMGB1 expression in the ERK1/2- and Akt-dependent manners in DLD-1 cells. HMGB1 gene knockdown enhanced the cytotoxicity and cell growth inhibition of OXA. Moreover, OXA-increased HMGB1 expression was by inducing NF-κB-DNA-binding activity to in DLD-1 cells. Compared to a single agent, OXA combined with metformin administration resulted in cytotoxicity and cell growth inhibition synergistically, accompanied with reduced HMGB1 level. These findings may have implications for the rational design of future drug regimens incorporating OXA and metformin for the treatment of CRC.

show abstract

Downregulation of NPM expression by Her-2 reduces resistance of gastric cancer to oxaliplatin

Cited by 7 publications

References 45 publications

Oncogene c‐fos and mutant R175H p53 regulate expression of Nucleophosmin implicating cancer manifestation

Oncogene c‐fos and mutant R175H p53 regulate expression of Nucleophosmin implicating cancer manifestation

Caveolin-1 Promotes Chemoresistance of Gastric Cancer Cells to Cisplatin by Activating WNT/β-Catenin Pathway

Metformin increases the cytotoxicity of oxaliplatin in human DLD‐1 colorectal cancer cells through down‐regulating HMGB1 expression

Contact Info

Product

Resources

About