PSPC1 mediates TGF-β1 autocrine signalling and Smad2/3 target switching to promote EMT, stemness and metastasis

Yeh, Hsi Wen; Hsu, En‐Chi; Lee, Szu Shuo; Lang, Yaw-Dong; Lin, Yuh‐Charn; Chang, Chieh Yu; Lee, Suz Yi; Gu, De Leung; Shih, Jou-Ho; Ho, Chun Ming; Chen, Chian Feng; Chen, Chiung Tong; Tu, Pang Hsien; Cheng, Ching Feng; Chen, Ruey‐Hwa; Yang, Ruey‐Bing; Jou, Yuh–Shan

doi:10.1038/s41556-018-0062-y

Cited by 156 publications

(161 citation statements)

References 63 publications

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“…A NSCLC cell line, A549 (ATCC ® CCL-185™), was obtained from American Type Culture Collection (ATCC). 27,28 Cells were cultured in the Roswell Park Memorial Institute medium (RPMI 1640, Gibco) with 10% fetal bovine serum (FBS, Gibco), and in a humidified 5% CO 2 incubator at 37°C. The subculture process was performed two times every week.…”

Section: Cell Culturementioning

confidence: 99%

<p>Fullerene Derivatives as Lung Cancer Cell Inhibitors: Investigation of Potential Descriptors Using QSAR Approaches</p>

Huang¹,

Kraevaya²,

Voronov³

et al. 2020

IJN

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Background: Nanotechnology-based strategies in the treatment of cancer have potential advantages because of the favorable delivery of nanoparticles into tumors through porous vasculature. Materials and Methods: In the current study, we synthesized a series of water-soluble fullerene derivatives and observed their anti-tumor effects on human lung carcinoma A549 cell lines. The quantitative structure-activity relationship (QSAR) modeling was employed to investigate the relationship between anticancer effects and descriptors relevant to peculiarities of molecular structures of fullerene derivatives. Results: In the QSAR regression model, the evaluation results revealed that the determination coefficient r 2 and leave-one-out cross-validation q 2 for the recommended QSAR model were 0.9966 and 0.9246, respectively, indicating the reliability of the results. The molecular modeling showed that the lack of chlorine atom and a lower number of aliphatic single bonds in saturated hydrocarbon chains may be positively correlated with the lung cancer cytotoxicity of fullerene derivatives. Synthesized water-soluble fullerene derivatives have potential functional groups to inhibit the proliferation of lung cancer cells. Conclusion: The guidelines obtained from the QSAR model might strongly facilitate the rational design of potential fullerene-based drug candidates for lung cancer therapy in the future.

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Section: Cell Culturementioning

confidence: 99%

<p>Fullerene Derivatives as Lung Cancer Cell Inhibitors: Investigation of Potential Descriptors Using QSAR Approaches</p>

Huang¹,

Kraevaya²,

Voronov³

et al. 2020

IJN

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“…(52). Paraspeckle component 1 promote EMT and metastasis through TGF-b sigaling (53). Recently, it was reported that the PI3K-Akt signaling pathway also plays an important role in EMT.…”

Section: Ra Is a Metabolic Intermediate Of Vitamin A And Atramentioning

confidence: 99%

APLNR is involved in ATRA‐induced growth inhibition of nasopharyngeal carcinoma and may suppress EMT through PI3K‐Akt‐mTOR signaling

Liu¹,

Liu²,

Chen³

et al. 2019

The FASEB Journal

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The apelin receptor (APLNR) is a GPCR involved in many pathophysiological processes; however, the correlation between APLNR expression and nasopharyngeal carcinoma (NPC) has not been reported. In this study, we used cDNA microarray data to determine APLNR expression levels in NPC tissues. We found that APLNR expression was reduced in NPC tissues compared with noncancerous nasopharyngeal epithelial tissues. Subsequently, a large‐scale sample of 1015 tissues was used to validate this discovery and explore the relationship between APLNR expression and prognosis of NPC. Expression levels of APLNR in NPC tissues were indeed down‐regulated. Furthermore, positive expression of APLNR in NPC predicted a better prognosis (disease‐free survival: P = 0.001; overall survival: P < 0.001). Moreover, ingenuity pathway analysis revealed that an indirect interaction existed between APLNR and retinoic acid (RA) in the cancer regulatory network. Consistently, after treatment with all‐trans‐RA (ATRA), we found that APLNR was significantly up‐regulated in NPC cell lines (5‐8F and HNE1), and proliferation of NPC cells was inhibited. Cell cycle arrest occurred in the G0/G1 phase. In contrast, knockdown of APLNR diminished ATRA‐induced growth inhibition of NPC cells. In addition, we surprisingly found that APLNR also played an important role in migration and invasion of NPC. Wound‐healing and Transwell assays revealed that APLNR overexpression led to reduced migratory and invasive properties in 2 NPC cell lines. Western blot results revealed that hallmarks of epithelial‐mesenchymal transition (EMT) were altered as well, suggesting that APLNR was capable of inhibiting EMT in NPC cells. Our study further demonstrated that low expression of APLNR promoted EMT in NPC cells by activating the PI3K‐protein kinase B‐mammalian target of rapamycin signaling pathway. Taken together, our data suggest that APLNR could potentially predict prognosis for patients with NPC and inhibit proliferation, migration, invasion, and EMT in nasopharyngeal cancer cells.—Liu, Y., Liu, Q., Chen, S., Liu, Y., Huang Y., Chen, P., Li, X., Gao, G., Xu, K., Fan, S., Zeng Z., Xiong W., Tan, M., Li, G., Zhang W. APLNR is involved in ATRA‐induced growth inhibition of nasopharyngeal carcinoma and may suppress EMT through PI3K‐Akt‐mTOR signaling. FASEB J. 33, 11959‐11972 (2019). http://www.fasebj.org

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“…We found that 2266 genes are overexpressed in the ADPA tumours, including the crucial oncogenic driver genes KRAS , MDM2 , PDGFA , BCL2L11 , IL6ST , SMAD2 , CCND1 , LEF1 , VEGFA , RAF1 , CDK6 or CDK4 . These genes play essential roles in tumourigenesis and the development of various types of cancer.…”

Section: Discussionmentioning

confidence: 93%

Gene expression profiling in aggressive digital papillary adenocarcinoma sheds light on the architecture of a rare sweat gland carcinoma

et al. 2019

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Background Sweat gland carcinomas are rare cutaneous adnexal malignancies. Aggressive digital papillary adenocarcinoma (ADPA) represents a very rare subentity, thought to arise almost exclusively from the sweat glands of the fingers and toes. The aetiology of sweat gland carcinomas and ADPA is largely unknown. ADPAs are most likely driven by somatic mutations. However, somatic mutation patterns are largely unexplored, creating barriers to the development of effective therapeutic approaches to the treatment of ADPA. Objectives To investigate the transcriptome profile of ADPA using a sample of eight formalin-fixed, paraffin-embedded tissue samples of ADPA and healthy control tissue. Methods Transcriptome profiling was performed using the Affymetrix PrimeView Human Gene Expression Microarray and findings were validated via reverse transcription of RNA and real-time quantitative polymerase chain reaction. Results Transcriptome analyses showed increased tumour expression of 2266 genes, with significant involvement of cell cycle, ribosomal and crucial cancer pathways. Our results point to tumour overexpression of FGFR2 (P = 0Á001). Conclusions The results indicate the involvement of crucial oncogenic driver pathways, highlighting cell cycle and ribosomal pathways in the aetiology of ADPA. Suggested tumour overexpression of FGFR2 raises the hope that targeting the fibroblast growth factor (FGF)/FGF receptor axis might be a promising treatment for ADPA and probably for the overall group of sweat gland carcinomas. What's already known about this topic?• Aggressive digital papillary adenocarcinoma (ADPA) is a rare sporadic tumour, arising predominantly from sweat glands of fingers or toes.• ADPA is characterized by a local aggressive behaviour, a high recurrence rate and an emerging metastatic potential.• ADPA is most probably driven by somatic mutations. However, somatic mutation patterns are largely unexplored.• Knowledge of the biology of ADPA is almost completely lacking, creating barriers to the development of effective therapy strategies. Gene expression profiling in aggressive digital papillary adenocarcinoma, H.M. Surowy et al. 1153 a Paired t-test [cycle threshold (DCt) of tumour and control tissue]. b Not reliably detected in >1 ADPA tumours. Gene expression profiling in aggressive digital papillary adenocarcinoma, H.M. Surowy et al. 1155Fig 4.Differentially expressed genes (P < 0Á05, P detection < 0Á05, ratio < 0Á67 or > 1Á5) associated with the gene ontology (GO) 'angiogenesis' (GO:0001525) were subjected to cluster analysis and the resulting heatmaps and dendrograms show a clear separation of a tumour (T) and a normal tissue (N) cluster. Note: the official gene symbol for interleukin 8 is now CXCL8.

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PSPC1 mediates TGF-β1 autocrine signalling and Smad2/3 target switching to promote EMT, stemness and metastasis

Cited by 156 publications

References 63 publications

<p>Fullerene Derivatives as Lung Cancer Cell Inhibitors: Investigation of Potential Descriptors Using QSAR Approaches</p>

<p>Fullerene Derivatives as Lung Cancer Cell Inhibitors: Investigation of Potential Descriptors Using QSAR Approaches</p>

APLNR is involved in ATRA‐induced growth inhibition of nasopharyngeal carcinoma and may suppress EMT through PI3K‐Akt‐mTOR signaling

Gene expression profiling in aggressive digital papillary adenocarcinoma sheds light on the architecture of a rare sweat gland carcinoma

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