CUL4A Induces Epithelial–Mesenchymal Transition and Promotes Cancer Metastasis by Regulating ZEB1 Expression

Wang, Yunshan; Wen, Mingxin; Kwon, Yong-Won; Xu, Yangyang; Liu, Yueyong; Zhang, Pengju; He, Xiaohui; Wang, Qin; Huang, Yurong; Jen, Kuang-Yu; LaBarge, Mark A.; Li, You; Kogan, Scott C.; Gray, Joe W.; Mao, Jian‐Hua; Wei, Guangwei

doi:10.1158/0008-5472.can-13-2182

Cited by 177 publications

(169 citation statements)

References 31 publications

(40 reference statements)

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“…2,3 Greater understanding of the multiple biochemical pathways involved in the molecular pathogenesis of lung cancer is crucial to the development of treatment strategies that can target molecular aberrations and their downstream activated pathways. 4,5 Identification of the molecular markers determining the risk of occurrence and progression and approaches for therapeutic treatment of lung cancer are the most significantly important problems in molecular oncology.…”

Section: Introductionmentioning

confidence: 99%

Overexpression of TRIM25 in Lung Cancer Regulates Tumor Cell Progression

Qin

Zhang

2016

Technol Cancer Res Treat

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Lung cancer is one of the most common causes of cancer-related deaths worldwide. Although great efforts and progressions have been made in the study of the lung cancer in the recent decades, the mechanism of lung cancer formation remains elusive. To establish effective therapeutic methods, new targets implied in lung cancer processes have to be identified. Tripartite motifcontaining 25 has been associated with ovarian and breast cancer and is thought to positively promote cell growth by targeting the cell cycle. However, whether tripartite motif-containing 25 has a function in lung cancer development remains unknown. In this study, we found that tripartite motif-containing 25 was overexpressed in human lung cancer tissues. Expression of tripartite motifcontaining 25 in lung cancer cells is important for cell proliferation and migration. Knockdown of tripartite motif-containing 25 markedly reduced proliferation of lung cancer cells both in vitro and in vivo and reduced migration of lung cancer cells in vitro. Meanwhile, tripartite motif-containing 25 silencing also increased the sensitivity of doxorubicin and significantly increased death and apoptosis of lung cancer cells by doxorubicin were achieved with knockdown of tripartite motif-containing 25. We also observed that tripartite motif-containing 25 formed a complex with p53 and mouse double minute 2 homolog (MDM2) in both human lung cancer tissues and in lung cancer cells and tripartite motif-containing 25 silencing increased the expression of p53. These results provide evidence that tripartite motif-containing 25 contributes to the pathogenesis of lung cancer probably by promoting proliferation and migration of lung cancer cells. Therefore, targeting tripartite motif-containing 25 may provide a potential therapeutic intervention for lung cancer.

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Section: Introductionmentioning

confidence: 99%

Overexpression of TRIM25 in Lung Cancer Regulates Tumor Cell Progression

Qin

Zhang

2016

Technol Cancer Res Treat

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“…Epithelial-to-mesenchymal transition (EMT) serves as a pivotal role in the invasion of various cancer cells by the transformation of polarized and adherent epithelial cells into motile and invasive mesenchymal cells [12,13]. Many transcription factors involved in EMT such as Snail and Twist upregulate the expression of mesenchymal markers such as vimentin, collagen, fibronectin and downregulate the expression of epithelial markers such as E-cadherin.…”

Section: Introductionmentioning

confidence: 99%

Downregulation of miR‐638 promotes invasion and proliferation by regulating SOX2 and induces EMT in NSCLC

Xia

Liu

et al. 2014

FEBS Letters

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Edited by Tamas DalmayKeywords: miR-638 SRY (sex determining region Y)-box 2 Proliferation Invasion Epithelial-to-mesenchymal transition Non-small-cell lung cancer a b s t r a c t Aberrant expression of microRNAs has been shown to regulate the biological processes of lung cancer cells. However, the role of miR-638 in the development of NSCLC is still unclear. In this study, low miR-638 and high SOX2 were shown to be associated with tumor size and metastasis of NSCLC patients. Downregulated miR-638 could promote cell invasion and proliferation, while high miR-638 expression reversed the effect. Furthermore, miR-638 could regulate SOX2 by directly binding to its 3 0 -UTR. Silencing of SOX2 by siRNA partially abolished the enhancement of cell invasion and proliferation induced by downregulated miR-638. Aberrant miR-638 expression could modulate the expression levels of markers of epithelial-to-mesenchymal transition. Our results indicate that miR-638 may play a pivotal role in the development of NSCLC.

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“…IHC staining was used to detect the expression of CUL4A in human OS, indicating increased expression of CUL4A in OS tissues compared to that in the ANCT. transition, and metastasis of breast cancer through regulation of ZEB1 expression and antitumor immune response, 19,20 enhances tumor growth and sensitizes lung cancer cells to erlotinib via regulation of EGFR 21 and determines the response to thalidomide treatment in prostate cancer, 22 involving in the multi-drug resistance in cancer. 23 Inhibition of CUL4A expression can augment DNA damage response and fight against the progression of skin cancer.…”

Section: Discussionmentioning

confidence: 99%

Knockdown of CUL4A inhibits invasion and induces apoptosis in osteosarcoma cells

Song

Zhang

Shao

2015

Int J Immunopathol Pharmacol

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Cullin4A (CUL4A) is implicated in many cellular events including cell survival and growth. However, the specific function and underlying mechanisms of CUL4A in cancer invasion have not yet been elucidated. In this work, we were focused on investigating the role of CUL4A in human osteosarcoma (OS). The expression level of CUL4A was evaluated by immunohistochemical (IHC) assay in human OS tissues. Lentivirus-mediated CUL4A shRNA (Lv-shCUL4A) constructed by us was transfected into OS cells for assessing its effects on cell proliferation and invasive potential, respectively detected by MTT and Transwell assays. It was demonstrated that the expression of CUL4A protein was markedly increased in OS tissues compared with the adjacent non-cancerous tissues (ANCT) (57.8% vs. 25.6%, P = 0.019), and was associated with the distant metastases in OS patients (P = 0.016). In vitro, silencing of CUL4A gene inhibited OS cell proliferation and invasion, and induced cell apoptosis, followed by increased expression of p27 and p53 and decreased expression of MMP-2. Therefore, these findings indicate that elevated expression of CUL4A is positively correlated with distant metastases in OS patients, and knockdown of CUL4A suppresses invasion and induces apoptosis in OS cells, suggesting that CUL4A may serve as a potential target for the treatment of OS.

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CUL4A Induces Epithelial–Mesenchymal Transition and Promotes Cancer Metastasis by Regulating ZEB1 Expression

Cited by 177 publications

References 31 publications

Overexpression of TRIM25 in Lung Cancer Regulates Tumor Cell Progression

Overexpression of TRIM25 in Lung Cancer Regulates Tumor Cell Progression

Downregulation of miR‐638 promotes invasion and proliferation by regulating SOX2 and induces EMT in NSCLC

Knockdown of CUL4A inhibits invasion and induces apoptosis in osteosarcoma cells

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