Increased Expression of EIF5A2, Via Hypoxia or Gene Amplification, Contributes to Metastasis and Angiogenesis of Esophageal Squamous Cell Carcinoma

Li, Yan; Fu, Li; Li, Jian Biao; Qin, Yanru; Zeng, Ting; Zhou, Jie; Zeng, Zhao Lei; Chen, Jinna; Cao, Ting; Ban, Xiaohua; Qian, Chao‐Nan; Cai, Zongwei; Xie, Dan; Huang, Peng; Guan, Xin Yuan

doi:10.1053/j.gastro.2014.02.029

Cited by 93 publications

(123 citation statements)

References 23 publications

Supporting

Mentioning

117

Contrasting

Unclassified

Order By: Relevance

“…EIF5A2 has been implicated in a number of cancers, including bladder cancer, colorectal cancer, pancreatic adenocarcinoma, esophageal squamous cell carcinoma, gastric adenocarcinoma, breast cancer, prostate adenocarcinoma, hepatocellular carcinoma, ovarian cancer and melanoma (9,(14)(15)(16)(17)(18)(19)(20)(21)(22). Patients with esophageal squamous cell carcinoma, bladder cancer and pancreatic adenocarcinoma in which EIF5A2 is overexpressed have been demonstrated to exhibit statistically significantly shorter survival times (14,17,20).…”

Section: Discussionmentioning

confidence: 99%

“…Patients with esophageal squamous cell carcinoma, bladder cancer and pancreatic adenocarcinoma in which EIF5A2 is overexpressed have been demonstrated to exhibit statistically significantly shorter survival times (14,17,20). Furthermore, patients with hepatocellular carcinoma in which EIF5A2 is overexpressed have a greater number of metastases and are more likely to present with venous invasion (23,24).…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, any compound that increases miR-30b and/or miR-125b transcription has the potential to serve as a successful therapy for NSCLC. In addition, the compound N1-guanyl-1,7-diaminoheptane (GC7) is a direct EIF5A2 inhibitor and therefore has the potential to be an effective therapy for NSCLC (17)(18)(19)21).…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Knockdown of EIF5A2 inhibits the malignant potential of non-small cell lung cancer cells

Chen

Zhang

et al. 2018

Oncol Lett

View full text Add to dashboard Cite

Abstract. Eukaryotic translation initiation factor 5A2(EIF5A2) has been demonstrated to be upregulated in numerous types of human cancer and is associated with cancer progression. However, the expression and role of EIF5A2 in non-small cell lung cancer (NSCLC) remains unclear. In the present study, the role of EIF5A2 in NSCLC was investigated, in addition to the underlying molecular mechanisms by which EIF5A2 acts. Relative EIF5A2 expression levels were determined in NSCLC cells and compared with levels in non-cancerous lung tissues. Short interfering (si)RNA targeted against EIF5A2 was used to knock down EIF5A2 levels in NSCLC cells. Cell proliferation, apoptosis rate, migration ability and invasion ability were determined in untreated and siRNA-treated NSCLC cells, in addition to the relative protein expression levels of various tumorigenic proteins and E-cadherin. EIF5A2 expression was significantly higher in NSCLC tissues compared with adjacent normal tissues. Knockdown of EIF5A2 in the NSCLC cells significantly inhibited cell proliferation and induced apoptosis. Furthermore, EIF5A2 silencing suppressed cell migratory and invasive capacities in vitro. Silencing of EIF5A2 in the NSCLC cells resulted in the downregulation of the tumorigenic proteins, apoptosis regulator Bcl-2 and myc proto-oncogene protein, and upregulation of E-cadherin, suggesting that EIF5A2 promotes proliferation and metastasis through these proteins. EIF5A2 may therefore serve as a novel therapeutic target for the treatment of NSCLC.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Knockdown of EIF5A2 inhibits the malignant potential of non-small cell lung cancer cells

Chen

Zhang

et al. 2018

Oncol Lett

View full text Add to dashboard Cite

show abstract

“…As shown in Figure 6d, after FV-429 treatment, the protein expression ratios of p-Src/c-Src and p-Stat3/Stat3 and HIF-1α expression decreased in hypoxic tumor tissues (the central part of tumors and normoxic tumor tissues referred to the outer part of tumors 21 ), and IHC study (Figure 6e) showed the expression of c-Src and HIF-1α and nuclear translocation of Stat3 decreased in the tissues. Toxicological assessment.…”

mentioning

confidence: 89%

Influence of c-Src on hypoxic resistance to paclitaxel in human ovarian cancer cells and reversal of FV-429

Guo

Liao

et al. 2018

Cell Death Dis

View full text Add to dashboard Cite

SRC family kinase was documented to have vital roles in adjusting cancer cell malignant behaviors. To date, the role of c-Src, a member of SRC family kinase, in resistance to paclitaxel in human ovarian cancer cells under hypoxia has not been investigated. In the present study, we discovered that hypoxic environment suppressed paclitaxel-induced G2/M phase arrest and blockade of c-Src improved ovarian cancer cells' sensitivity to paclitaxel. FV-429, a derivative of natural flavonoid wogonin, could suppress gene expression and activation of c-Src, followed by deteriorated Stat3 nuclear translocation and its binding to HIF-1α, resulting in paclitaxel resistance reversal through G2/M arrest potentiation. Our study demonstrated that c-Src contributed to hypoxic microenvironment-rendered paclitaxel resistance in human epithelial ovarian cancer cells by G2/M phase arrest deterioration, and through c-Src suppression, FV-429 was capable of reversing the resistance by blocking c-Src/Stat3/HIF-1α pathway. Cell Death and Disease (2018) 8, e3178; doi:10.1038/cddis.2017.367; published online 11 January 2018In solid tumor, cells in hypoxic region becomes resistant to chemotherapy and radiotherapy, the reason for which is that hypoxia helps cancer cells survive by inducing several genes involved that accelerate the progression of malignancy. 1Physiological hypoxia occurs when the oxygen tension falls below 2%, thus a cultivating environment containing 1% oxygen is commonly used to mimic hypoxic environment in vitro.2-5 Ovarian cancer is a common gynecological cancer and one of the lethal cause of death from gynecological malignancy; 6 however, failure or relapse always exists due to the emergence of constant resistance. It has been reported that around 69% ovarian tumors from patients overexpress hypoxia inducible factor-1α (HIF-1α), 7,8 indicating that hypoxia may be closely related to ovarian tumors. Study showed that hypoxia increased G0/G1 phase percentage in ovarian cancer cells.9 However, the effect of paclitaxel is based on the inhibition of microtubule depolymerization, leading to G2/M phase arrest in cancer cells, which can be weakened by the effect induced by hypoxia. Considering on the uncertainty, the resistance to paclitaxel is probably due to G1 phase promotion rendered by hypoxic environment. However, the inner mechanism of the regulation on this cell cycle arrest still remains unclear.Non-receptor tyrosine kinase c-Src seems to be associated with hypoxia.1,10-12 Signal transducer and activator of transcription 3 (Stat3), a transcription factor having vital roles in malignancy, can be activated by c-Src. 13 Mccann et al.14 found that Stat3 activation contributed to hypoxia-induced resistance. Moreover, Huang et al. 9 found that blocking HIF-1α can improve G2/M arrest induced by paclitaxel under hypoxia.Thus we supposed that c-Src/Stat3/HIF-1α axis may regulate hypoxic resistance to paclitaxel under hypoxia.FV-429, a derivative of wogonin, which is one of the main components extracted from Scutellaria baicalensis...

show abstract

“…Recently studies found that EIF5A2 was aberrantly expressed in several types of tumor cells, including ovarian cancer, bladder cancer, hepatocellular carcinoma and colon cancer [15][16]29]. Further investigation demonstrated its involvement with the proliferation, invasion, metastasis and chemoresistance of tumor cells [13,30]. Thus, eIF5A2, located on chromosome 3q, has been characterized as a novel oncogene.…”

Section: The Doxorubicin-induced Emt Can Be Reversed By Gc7 In Er-negmentioning

confidence: 99%

N1-Guanyl-1,7-Diaminoheptane Sensitizes Estrogen Receptor Negative Breast Cancer Cells to Doxorubicin by Preventing Epithelial-Mesenchymal Transition through Inhibition of Eukaryotic Translation Initiation Factor 5A2 Activation

Liu¹,

Liu

Fu³

et al. 2015

Cell Physiol Biochem

View full text Add to dashboard Cite

Background: Approximately 30% of breast cancer does not express the estrogen receptor (ER), which is necessary for endocrine-based therapy approaches. Many studies demonstrated that eukaryotic translation initiation factor 5A2 (eIF5A2) serves as a proliferation-related oncogene in tumorigenic processes. Methods: The present study used cell viability assays, EdU incorporation assays, western blot, and immunofluorescence to explore whether N1-guanyl-1,7-diaminoheptane (GC7), which inhibits eIF5A2 activation, exerts synergistic cytotoxicity with doxorubicin in breast cancer. Results: We found that GC7 enhanced doxorubicin cytotoxicity in ER-negative HCC1937 cells but had little effect in ER-positive MCF-7 and Bcap-37 cells. Administration of GC7 reversed the doxorubicin-induced epithelial-mesenchymal transition (EMT) in ER-negative breast cancer cells. Knockdown of eIF5A2 by siRNA inhibited the doxorubicin-induced EMT in ER-negative HCC1937 cells. Conclusion: These data demonstrated that GC7 combination therapy may enhance the therapeutic efficacy of doxorubicin in estrogen negative breast cancer cells by preventing EMT through inhibition of eIF5A2 activation.

show abstract

Increased Expression of EIF5A2, Via Hypoxia or Gene Amplification, Contributes to Metastasis and Angiogenesis of Esophageal Squamous Cell Carcinoma

Cited by 93 publications

References 23 publications

Knockdown of EIF5A2 inhibits the malignant potential of non-small cell lung cancer cells

Knockdown of EIF5A2 inhibits the malignant potential of non-small cell lung cancer cells

Influence of c-Src on hypoxic resistance to paclitaxel in human ovarian cancer cells and reversal of FV-429

N1-Guanyl-1,7-Diaminoheptane Sensitizes Estrogen Receptor Negative Breast Cancer Cells to Doxorubicin by Preventing Epithelial-Mesenchymal Transition through Inhibition of Eukaryotic Translation Initiation Factor 5A2 Activation

Contact Info

Product

Resources

About