PHD3 Controls Lung Cancer Metastasis and Resistance to EGFR Inhibitors through TGFα

Dopeso, Higinio; Jiao, Huike; Cuesta, Ángel M.; Henze, Anne-Theres; Jurida, Liane; Acker‐Palmer, Amparo; Garvalov, Boyan K.; Acker, Till

doi:10.1158/0008-5472.can-17-1346

Cited by 44 publications

(29 citation statements)

References 48 publications

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“…For colony formation assay, cells were exposed to CT-707 under normoxia or hypoxia for 24 hours, then trypsinized and re-plated at a density of 500 living cells/well in six-well plates. Two weeks later, cells were stained with crystal violet solution and the number of colonies having more than 50 cells were counted (10). For apoptosis detection, cells treated with CT-707 were analyzed after staining with PI solution (#ZF-50-0001; Multi Sciences, Ltd.), on a FACS Calibur cytometer (Becton Dickinson; ref.…”

Section: Sulforhodamine B Assay Colony Formation Assay and Flow Cytmentioning

confidence: 99%

Multikinase Inhibitor CT-707 Targets Liver Cancer by Interrupting the Hypoxia-Activated IGF-1R–YAP Axis

et al. 2018

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Given that Yes-associated protein (YAP) signaling acts as a critical survival input for hypoxic cancer cells in hepatocellular carcinoma (HCC), disruption of YAP function and the maintenance of hypoxia is an attractive way to treat HCC. Utilizing a cell-based YAP-TEAD luciferase reporter assay and functional analyses, we identified CT-707, a China-FDA approved multi-kinase inhibitor under clinical trial with remarkable inhibitory activity against YAP function. CT-707 exhibited prominent cytotoxicity under hypoxia on HCC cells, which was attributable to the inhibition of YAP signaling. CT-707 arrested tumor growth in HepG2, Bel-7402, and HCC patient-derived xenografts. Mechanistically, the inhibitory activity of CT-707 on YAP signaling was due to the interruption of hypoxia-activated IGF1R. Overall, these findings not only identify CT-707 as a promising hypoxia-targeting agent against HCC, but they also unveil IGF1R as a new modulator specifically regulating hypoxia-activated YAP signaling. CT-707 may represent a novel clinical approach for patients with HCC suffering poor drug response due to intratumor hypoxia. .

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Section: Sulforhodamine B Assay Colony Formation Assay and Flow Cytmentioning

confidence: 99%

Multikinase Inhibitor CT-707 Targets Liver Cancer by Interrupting the Hypoxia-Activated IGF-1R–YAP Axis

et al. 2018

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“…Lung cancer is the leading cause of cancer-related death worldwide, with a propensity for distant metastasis. Better understanding of the molecular events that regulate the development of lung cancer metastasis and biomarkers that predict which patients will experience metastasis are needed to improve survival rates (24). It has been reported that cancer cells secrete EVs that can be easily isolated from various body fluids (25) and which contain cancer-specific contents.…”

Section: Discussionmentioning

confidence: 99%

Extracellular vesicle tetraspanin-8 level predicts distant metastasis in non–small cell lung cancer after concurrent chemoradiation

Liu

Fan

et al. 2020

Sci. Adv.

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Non–small cell lung cancer (NSCLC) is the most commonly diagnosed cancer and the leading cause of cancer death worldwide. More than half of patients with NSCLC die after developing distant metastases, so rapid, minimally invasive prognostic biomarkers are needed to reduce mortality. We used proteomics to identify proteins differentially expressed on extracellular vesicles (EVs) of nonmetastatic 393P and metastatic 344SQ NSCLC cell lines and found that tetraspanin-8 (Tspan8) was selectively enriched on 344SQ EVs. NSCLC cell lines treated with EVs overexpressing Tspan8 also exhibited increased Matrigel invasion. Elevated Tspan8 expression on serum EVs of individuals with stage III premetastatic NSCLC tumors was also associated with reduced distant metastasis–free survival, suggesting that Tspan8 levels on serum EVs may predict future metastasis. This result suggests that a minimally invasive blood test to analyze EV expression of Tspan8 may be of potential value to guide therapeutic decisions for patients with NSCLC and merits further study.

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“…Our previous study has suggested that miR-152-3p suppressed PC cells migration and invasion by downregulating TGF-α [14]. The aberrant expression of TGF-α and TGF-α-induced signaling was involved in the progression and metastasis of various carcinomas [25][26][27]. TGF-α was found to bind to EGFR ligands and activate EGFR by inducing EGFR tyrosine autophosphorylation [28].…”

Section: Discussionmentioning

confidence: 99%

Circular RNA circANKS1B as the Sponge of miR-152-3p Promotes Prostate Cancer Progression by up-Regulating TGF-α Expression

Liu

Pan

Wang

et al. 2020

Preprint

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Background: Growing studies indicate that circRNAs play critical roles in human diseases, and show great potential as biomarkers and therapeutic targets. This study aims to investigate the expression and function of circANKS1B in prostate cancer (PC).Methods: The expression of circANKS1B and miRNA-152-3p were determined by real-time qRT-PCR. The cell migration and invasion were measured by transwell assay. The interaction between circANKS1B and miR-152-3p was confirmed by dual-luciferase reporter gene assay. Rescue experiments were conducted to demonstrate whether circANKS1B regulated the migration and invasion of PC cells by the circANKS1B-miR-152-3p-TGF-α pathway.Results: The expression of circANKS1B was dramatically up-regulated both in PC cells and tissues. Moreover, high circANKS1B expression was associated with a poor prognosis of PC patients. Dual-luciferase reporter assay indicated that circABKS1B directly bound to miRNA-152-3p. Furthermore, circANKS1B negatively regulated miR-152-3p expression. Knockdown of circANKS1B remarkably suppressed PC cells invasion and TGF-α expression, while the effects of circANKS1B silencing were reversed by miR-152-3p deficiency. In addition, the impact of miR-152-3p silencing on PC cell invasion was also abrogated by TGF-α deficiency. In all, circANKS1B as the sponge of miR-152-3p promotes prostate cancer progression by up-regulating TGF-α expression.Conclusion: Our findings reveal that circANKS1B could be a potential prognostic biomarker and therapeutic target of PC.

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PHD3 Controls Lung Cancer Metastasis and Resistance to EGFR Inhibitors through TGFα

Cited by 44 publications

References 48 publications

Multikinase Inhibitor CT-707 Targets Liver Cancer by Interrupting the Hypoxia-Activated IGF-1R–YAP Axis

Multikinase Inhibitor CT-707 Targets Liver Cancer by Interrupting the Hypoxia-Activated IGF-1R–YAP Axis

Extracellular vesicle tetraspanin-8 level predicts distant metastasis in non–small cell lung cancer after concurrent chemoradiation

Circular RNA circANKS1B as the Sponge of miR-152-3p Promotes Prostate Cancer Progression by up-Regulating TGF-α Expression

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