Cyclin D1 promotes tumor cell invasion and metastasis by cytoplasmic mechanisms

Fusté, Noel P.; Ferrezuelo, Francisco; Garí, Eloi

doi:10.1080/23723556.2016.1203471

Cited by 14 publications

(16 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our in-silico analysis showing CDKN2B-AS1 shares regulatory miR-141 binding sites with cyclin-D1-D2 which was confirmed by luciferase and RIP assay. Cyclin-D1/D2 are also oncogenic in most cancers including RCC and play role in progression and metastasis 15,48,49 . Apart from the cell cycle regulation role of cyclin-D, it is also important in maintaining cellular adhesion, migration and metastasis through phosphorylation of paxillin and activation of Rac1 14,15,17 .…”

Section: Discussionmentioning

confidence: 99%

“…Cyclin-D1/D2 are also oncogenic in most cancers including RCC and play role in progression and metastasis 15,48,49 . Apart from the cell cycle regulation role of cyclin-D, it is also important in maintaining cellular adhesion, migration and metastasis through phosphorylation of paxillin and activation of Rac1 14,15,17 . Our results demonstrated that ectopic expression of miR-141 suppressed CDKN2B-AS1 and cyclin-D1/D2 expression in RCC cell lines.…”

Section: Discussionmentioning

confidence: 99%

“…[10][11][12][13] are common EMT phenomena. Often the progression of cancer through EMT is significantly induced by the interaction of Cyclin-D with its binding partner, Cdk4 which act as transcriptional regulators controlling cell proliferation and migration [14][15][16] . It is well known that Cyclin-D regulates the rate-limiting step in cell cycle progression from G1 to S phase.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

LncRNA CDKN2B-AS1/miR-141/cyclin D network regulates tumor progression and metastasis of renal cell carcinoma

et al. 2020

View full text Add to dashboard Cite

The molecular heterogeneity of renal cell carcinoma (RCC) complicates the therapeutic interventions for advanced metastatic disease and thus its management remains a significant challenge. This study investigates the role of the lncRNA CDKN2B-AS1 and miR-141-3p interactions in the progression and metastasis of kidney cancer. Human renal cancer cell lines (ACHN and Caki1), normal RPTEC cells, tissue cohorts, and a series of in vitro assays and in vivo mouse model were used for this study. An overexpression of CDKN2B-AS1 was observed in RCC compared to normal samples in TCGA and our in-house SFVAMC tissue cohorts. Reciprocally, we observed reduced expression of miR-141 in RCC compared to normal in the same cohorts. CDKN2B-AS1 shares regulatory miR-141 binding sites with CCND1 and CCND2 genes. Direct interactions of CDKN2B-AS1/miR-141/Cyclin D1-D2 were confirmed by RNA immunoprecipitation and luciferase reporter assays indicating that CDKN2B-AS1/miR-141/Cyclin D1-D2 acts as a ceRNA network in RCC. Functionally, attenuation of CDKN2B-AS1 and/or overexpression of miR-141 inhibited proliferation, clonogenicity, migration/invasion, induced apoptosis in vitro and suppressed tumor growth in xenograft mouse model. Further, overexpression of CDKN2B-AS1 is positively correlated with poor overall survival of RCC patients. Expression of miR-141 also robustly discriminated malignant from non-malignant tissues and its inhibition in normal RPTEC cells induced procancerous characteristics. CDKN2B-AS1 attenuation or miR-141 overexpression decreased CCND1/CCND2 expression, resulting in reduced RAC1/pPXN that are involved in migration, invasion and epithelial-mesenchymal transition. This study, for the first time, deciphered the role of CDKN2B-AS1/miR-141/Cyclin D axis in RCC and highlights this network as a promising therapeutic target for the regulation of EMT driven metastasis in RCC.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

LncRNA CDKN2B-AS1/miR-141/cyclin D network regulates tumor progression and metastasis of renal cell carcinoma

et al. 2020

View full text Add to dashboard Cite

show abstract

“…It exerts oncogenic functions through properties such as hyperactivation of CDK2 due to more stable LMW cyclin E/CDK2 complex formation [169], the resistance of LMW cyclin E/CDK2 complex to inhibitors p21 and p27 [170], altered substrate interactions [171], and cytoplasmic novel interactions that differ from the full-length cyclin E [172]. Like cytoplasmic LMW cyclin E, excessive cytoplasmic cyclin D1 also exerts oncogenic functions by promoting tumor cell invasion and metastasis [173][174][175] through cytoplasmic interactions [175,176].…”

Section: Cyclin Ementioning

confidence: 99%

Molecular crosstalk between cancer and neurodegenerative diseases

Seo

Park

2019

Cell. Mol. Life Sci.

View full text Add to dashboard Cite

The progression of cancers and neurodegenerative disorders is largely defined by a set of molecular determinants that are either complementarily deregulated, or share remarkably overlapping functional pathways. A large number of such molecules have been demonstrated to be involved in the progression of both diseases. In this review, we particularly discuss our current knowledge on p53, cyclin D, cyclin E, cyclin F, Pin1 and protein phosphatase 2A, and their implications in the shared or distinct pathways that lead to cancers or neurodegenerative diseases. In addition, we focus on the interdependent regulation of brain cancers and neurodegeneration, mediated by intercellular communication between tumor and neuronal cells in the brain through the extracellular microenvironment. Finally, we shed light on the therapeutic perspectives for the treatment of both cancer and neurodegenerative disorders. Keywords Age-related diseases • Cell death • Cell survival • Redox system • Glioma • Neurotoxicity Abbreviations Aβ Amyloid-β AD Alzheimer's disease ALS Amyotrophic lateral sclerosis AMPA α-Amino-3-hydroxy-5-methyl-4isoxazolepropionate APC/C Anaphase promoting complex/ cyclosome APP Amyloid precursor protein ATRA All-trans retinoic acid APL Acute promyelocytic leukemia Bax Bcl-2 associated X BH3 Bcl-2 homology 3 Bim Bcl-2-interacting mediator of cell death BimEL Bim-extra long CDK Cyclin-dependent kinase Cellular and Molecular Life Sciences

show abstract

“…The EGFR/HER2 signaling network is pivotal in controlling cancer proliferation and metastasis through the downstream effectors of AKT, ERK, and STAT3 [22][23][24]. Furthermore, hyperactivated HER2 signaling upregulates the cyclin D complex, promoting tumor cell invasion and metastasis [25,26]. Afatinib decreases phosphorylation between ErbB dimers more effectively than erlotinib and it has been reported to overcome therapy resistance to EGFR TKI in lung cancer clinically [27,28].…”

Section: Discussionmentioning

confidence: 99%

Targeting human epidermal growth factor receptor 2 enhances radiosensitivity and reduces the metastatic potential of Lewis lung carcinoma cells

et al. 2020

View full text Add to dashboard Cite

Background: Sublethal radiation induces matrix metalloproteinase 9 (MMP-9)-mediated radioresistance in Lewis lung carcinoma (LLC) cells and their metastatic dissemination. We aim to determine if EGFR/HER2 activation associates with MMP-9-mediated radioresistance and invasiveness in irradiated LLC cells. Methods: LLC cells were treated with erlotinib or afatinib followed by sublethal radiation. After irradiation, we examined the phosphorylation of EGFR/HER2 and MMP-9 expression. Colony formation assay determined if the kinase inhibitors sensitize LLC cells to radiation. Matrigel-coated Boyden chamber assay assessed cellular invasiveness. Resulting tumors of wild-type LLC cells or HER2 knock-down mutant cells were irradiated to induce pulmonary metastases. Results: Afatinib more effectively sensitized LLC cells to radiation and decreased invasiveness by inhibiting phosphorylation of EGFR, HER2, Akt, ERK, and p38, and down-regulating MMP-9 when compared to erlotinib. Afatinib abolished radiation-induced lung metastases in vivo. Furthermore, LLC HER2 knock-down cells treated with radiation had growth inhibition. Conclusion: Dual inhibition of radiation-activated EGFR and HER2 signaling by afatinib suppressed the proliferation and invasion of irradiated LLC cells. Increased radiosensitivity and decreased metastatic dissemination were observed by pharmacological or genetic HER2 inhibition in vivo. These findings indicate that HER2 plays a pivotal role in enhancing radioresistance and reducing metastatic potential of LLC cells.

show abstract

Cyclin D1 promotes tumor cell invasion and metastasis by cytoplasmic mechanisms

Cited by 14 publications

References 9 publications

LncRNA CDKN2B-AS1/miR-141/cyclin D network regulates tumor progression and metastasis of renal cell carcinoma

LncRNA CDKN2B-AS1/miR-141/cyclin D network regulates tumor progression and metastasis of renal cell carcinoma

Molecular crosstalk between cancer and neurodegenerative diseases

Targeting human epidermal growth factor receptor 2 enhances radiosensitivity and reduces the metastatic potential of Lewis lung carcinoma cells

Contact Info

Product

Resources

About