The CNPY2 enhances epithelial‐mesenchymal transition via activating the AKT/GSK3β pathway in non‐small cell lung cancer

Yu, Dou; Lei, Junqiang; Guo, Shunlin; Zhao, Da; Yue, Hongmei; Yu, Qin

doi:10.1002/cbin.10961

Cited by 14 publications

(10 citation statements)

References 29 publications

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“…We next analyzed the roles of miR-30a-3p and CNPY2 in regulating EMT in EKVX cells. Consistent with a previous report (25), our data showed that CNPY2 knockdown led to downregulation of N-cadherin protein and upregulation of E-cadherin expression (Fig. 4A), suggesting EMT suppression.…”

Section: Variablessupporting

confidence: 93%

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miR‑30a‑3p suppresses the proliferation and migration of lung adenocarcinoma cells by downregulating CNPY2

Wang

Kanmangne

et al. 2019

Oncol Rep

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Lung cancer is a leading cause of cancer-related morbidity and mortality worldwide. Although there are currently various therapeutic strategies including surgery, chemotherapy and radiotherapy, lung cancer still results in high mortality with a 5-year survival rate of less than 20%. The increasing need for new therapeutic targets and diagnostic/prognostic tools for lung cancer has promoted the demand for a better molecular and mechanistic understanding of its pathobiology. microRNA-30a-3p (miR-30a-3p) was recently recognized to be closely involved in the regulation of cancer cell invasion, migration and proliferation. However, the mechanistic role of miR-30a-3p in regulating the biological behavior of lung cancer, especially lung adenocarcinoma (LADC), is unknown. In the present study, we aimed to confirm the downregulation of miR-30a-3p in LADC tissues, and validate its functional impact on the pathogenesis of LADC via its molecular target, canopy fibroblast growth factor signaling regulator 2 (CNPY2), a known oncogene. Our data confirmed that CNPY2 was upregulated in LADC tissues, and the expression level of CNPY2 was correlated with the clinical outcomes of lung cancer patients. miR-30a-3p was confirmed as a key negative regulator of CNPY2 and reduced miR-30a-3p expression resulted in CNPY2 upregulation in LADC tissues. We then validated the functional outcome of miR-30a-3p in cancer pathobiology by the overexpression of miR-30a-3p in the LADC EKVX cell line. miR-30a-3p overexpression inhibited cancer cell proliferation, invasion and migration, by suppressing CNPY2 expression. In addition, miR-30a-3p inhibited epithelial-mesenchymal transition, a key feature of LADC, via CNPY2 suppression. Taken together, these findings suggest that miR-30a-3p exerts a novel inhibitory role in the pathogenesis of LADC via CNPY2 downregulation, and the miR-30a-3p/CNPY2 pathway is a potential therapeutic target for human LADC.

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Section: Variablessupporting

confidence: 93%

“…miR-30a-3p targets CNPY2 in regulating EMT-associated proteins in vitro. CNPY2 was reported to enhance epithelial-mesenchymal transition (EMT), an essential step of metastasis in NSCLC (25). We next analyzed the roles of miR-30a-3p and CNPY2 in regulating EMT in EKVX cells.…”

Section: Variablesmentioning

confidence: 99%

miR‑30a‑3p suppresses the proliferation and migration of lung adenocarcinoma cells by downregulating CNPY2

Wang

Kanmangne

et al. 2019

Oncol Rep

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“…Serine/threonine kinase (AKT) is closely related to the occurrence of EMT (15,16), and is involved in many biological and pathological processes, such as angiogenesis, invasion, and metastasis (17). In addition, the glycogen synthase kinase (GSK)-3β pathway is the classical downstream pathway of AKT, and often participates in the development of EMT with AKT (18). Furthermore, Snail expression can be regulated via the AKT/GSK-3β signaling pathway (19), and activation of this pathway may promote EMT in hepatoma cells (20) and ovarian clear cell carcinoma cells (21).…”

Section: Introductionmentioning

confidence: 99%

Resveratrol inhibits the invasion and metastasis of colon cancer through reversal of epithelial‑ mesenchymal transition via the AKT/GSK‑3β/Snail signaling pathway

Zhou

Huang

et al. 2019

Mol Med Report

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The identification of safe and effective drugs that inhibit tumor invasion and metastasis is required to improve the clinical outcome of patients with colon cancer. The present study aimed to investigate the inhibitory effects and possible mechanisms of action of resveratrol against the invasion and metastasis of colon cancer. AKT1-knockdown SW480 and SW620 colon cancer cells were used to detect the effects of resveratrol on cell invasion and metastasis, as well as changes in the expression of epithelial-mesenchymal transition (EMT) markers and serine/threonine kinase (AKT)/glycogen synthase kinase (GSK)-3β/Snail signaling pathway-related molecules in vitro . Furthermore, nude mice were inoculated with SW480 cells in the tail vein to establish an in vivo lung metastasis model of colon cancer, to investigate the effects of resveratrol on lung metastasis in colon cancer. The results revealed that resveratrol treatment and AKT1 knockdown significantly inhibited cell migration and invasion in colon cancer, and markedly increased E-cadherin expression and decreased that of N-cadherin, phospho (p)-AKT1, p-GSK-3β, and Snail in colon cancer both in vitro and in vivo . Furthermore, the effects of resveratrol were significantly weaker in the AKT1-knockdown cells. In conclusion, resveratrol may suppress the invasion and metastasis of colon cancer through reversal of EMT via the AKT/GSK-3β/Snail signaling pathway. AKT1 may therefore be a key regulator of EMT in colon cancer cells and a potential therapeutic target for this disease.

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“…M3 muscarinic acetylcholine receptors regulated EMT, perineural invasion, and metastasis in cholangiocarcinoma via the Akt pathway . Canopy homologue 2 promoted EMT via activating the Akt/GSK3 pathway in non–small‐cell lung cancer . The Akt signaling pathway mediated cigarette‐induced EMT in lung cancer .…”

Section: Small Molecules Against Emtmentioning

confidence: 87%

Small molecule inhibitors of epithelial‐mesenchymal transition for the treatment of cancer and fibrosis

Feng

Chen

Vaziri

et al. 2019

Medicinal Research Reviews

104

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Tissue fibrosis and cancer both lead to high morbidity and mortality worldwide; thus, effective therapeutic strategies are urgently needed. Because drug resistance has been widely reported in fibrotic tissue and cancer, developing a strategy to discover novel targets for targeted drug intervention is necessary for the effective treatment of fibrosis and cancer. Although many factors lead to fibrosis and cancer, pathophysiological analysis has demonstrated that tissue fibrosis and cancer share a common process of epithelial‐mesenchymal transition (EMT). EMT is associated with many mediators, including transcription factors (Snail, zinc‐finger E‐box‐binding protein and signal transducer and activator of transcription 3), signaling pathways (transforming growth factor‐β1, RAC‐α serine/threonine‐protein kinase, Wnt, nuclear factor‐kappa B, peroxisome proliferator‐activated receptor, Notch, and RAS), RNA‐binding proteins (ESRP1 and ESRP2) and microRNAs. Therefore, drugs targeting EMT may be a promising therapy against both fibrosis and tumors. A large number of compounds that are synthesized or derived from natural products and their derivatives suppress the EMT by targeting these mediators in fibrosis and cancer. By targeting EMT, these compounds exhibited anticancer effects in multiple cancer types, and some of them also showed antifibrotic effects. Therefore, drugs targeting EMT not only have both antifibrotic and anticancer effects but also exert effective therapeutic effects on multiorgan fibrosis and cancer, which provides effective therapy against fibrosis and cancer. Taken together, the results highlighted in this review provide new concepts for discovering new antifibrotic and antitumor drugs.

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The CNPY2 enhances epithelial‐mesenchymal transition via activating the AKT/GSK3β pathway in non‐small cell lung cancer

Cited by 14 publications

References 29 publications

miR‑30a‑3p suppresses the proliferation and migration of lung adenocarcinoma cells by downregulating CNPY2

miR‑30a‑3p suppresses the proliferation and migration of lung adenocarcinoma cells by downregulating CNPY2

Resveratrol inhibits the invasion and metastasis of colon cancer through reversal of epithelial‑ mesenchymal transition via the AKT/GSK‑3β/Snail signaling pathway

Small molecule inhibitors of epithelial‐mesenchymal transition for the treatment of cancer and fibrosis

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