Twist induces epithelial-mesenchymal transition and cell motility in breast cancer via ITGB1-FAK/ILK signaling axis and its associated downstream network

Yang, Jiajia; Hou, Yixuan; Zhou, Maosheng; Wen, Siyang; Zhou, Jian; Xu, Lixiang; Tang, Xi; Du, Yan‐e; Hu, Ping; Liu, Manran

doi:10.1016/j.biocel.2015.12.004

Cited by 80 publications

(62 citation statements)

References 48 publications

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“…It has been reported MMPs have something to do with EMT in cancer progression [38]. our experiment results supported the view that ILK is an important regulator of EMT [39]. Conversely, we demonstrated that RI affected the expressions of these EMT-related proteins in EJ cells, the results showed that over-expression of RI remarkably restrained EMT of EJ cells, which is in line with previous report [40].…”

Section: Discussionsupporting

confidence: 93%

Interplay between intergrin-linked kinase and ribonuclease inhibitor affects growth and metastasis of bladder cancer through signaling ILK pathways

Zhuang

Zhong

et al. 2016

J Exp Clin Cancer Res

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BackgroundIntegrin-linked kinase (ILK) is a multifunctional adaptor protein which is involved with protein signalling within cells to modulate malignant (cancer) cell movement, cell cycle, metastasis and epithelial–mesenchymal transition (EMT). Our previous experiment demonstrated that ILK siRNA inhibited the growth and induced apoptosis of bladder cancer cells as well as increased the expression of Ribonuclease inhibitor (RI), an important cytoplasmic protein with many functions. We also reported that RI overexpression inhibited ILK and phosphorylation of AKT and GSK3β. ILK and RI gene both locate on chromosome 11p15 and the two genes are always at the adjacent position of same chromosome during evolution, which suggest that ILK and RI could have some relationship. However, underlying interacting mechanisms remain unclear between them. Here, we postulate that RI might regulate ILK signaling pathway via interacting with ILK.MethodsCo-immunoprecipitation, GST pull-down and co-localization under laser confocal microscope assay were used to determine the interaction between ILK and RI exogenously and endogenously. Furthermore, we further verified that there is a direct binding between the two proteins by fluorescence resonance energy transfer (FRET) in cells. Next, The effects of interplay between ILK and RI on the key target protein expressions of PI3K/AKT/mTOR signaling pathway were determined by western blot, immunohistochemistry and immunofluorescence assay in vivo and in vitro. Finally, the interaction was assessed using nude mice xenograft model.ResultsWe first found that ILK could combine with RI both in vivo and in vitro by GST pull-down, co-immunoprecipitation (Co-IP) and FRET. The protein levels of ILK and RI revealed a significant inverse correlation in vivo and in vitro. Subsequently, The results showed that up-regulating ILK could increase cell proliferation, change cell morphology and regulate cell cycle. We also demonstrated that the overexpression of ILK remarkably promoted EMT and expressions of target molecules of ILK signaling pathways in vitro and in vivo. Finally, we found that ILK overexpression significantly enhanced growth, metastasis and angiogenesis of xenograft tumor; Whereas, RI has a contrary role compared to ILK in vivo and in vitro.ConclusionsOur findings, for the first time, directly proved that the interplay between ILK and RI regulated EMT via ILK/PI3K/AKT signaling pathways for bladder cancer, which highlights the possibilities that ILK/RI could be valuable markers together for the therapy and diagnosis of human carcinoma of urinary bladder.

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Section: Discussionsupporting

confidence: 93%

Interplay between intergrin-linked kinase and ribonuclease inhibitor affects growth and metastasis of bladder cancer through signaling ILK pathways

Zhuang

Zhong

et al. 2016

J Exp Clin Cancer Res

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“…The latest 12-Plex ‘DiLeu’ isobaric tags are cheaper as reagents can be readily synthesized in-house 47 unlike other members in these strategies. Both iTRAQ and TMT strategies have been broadly employed in cancer studies for drug discovery 49 , investigating cancer signaling 50 , as well as for investigating diagnostic and prognosis markers 51 . iTRAQ has also been employed to predict cancer recurrence and patient survival in triple negative breast tissue samples 52 .…”

Section: Quantitative Mass Spectrometry-based Proteomic Strategies Inmentioning

confidence: 99%

Advancement of mass spectrometry-based proteomics technologies to explore triple negative breast cancer

et al. 2017

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Understanding the complexity of cancer biology requires extensive information about the cancer proteome over the course of the disease. The recent advances in mass spectrometry-based proteomics technologies have led to the accumulation of an incredible amount of such proteomic information. This information allows us to identify protein signatures or protein biomarkers, which can be used to improve cancer diagnosis, prognosis and treatment. For example, mass spectrometry-based proteomics has been used in breast cancer research for over two decades to elucidate protein function. Breast cancer is a heterogeneous group of diseases with distinct molecular features that are reflected in tumour characteristics and clinical outcomes. Compared with all other subtypes of breast cancer, triple-negative breast cancer is perhaps the most distinct in nature and heterogeneity. In this review, we provide an introductory overview of the application of advanced proteomic technologies to triple-negative breast cancer research.

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“…miR-223 was shown to directly target integrin alpha 3 (ITGA3) and integrin β1 (ITGβ1) [100]. These integrins are involved in focal adhesion and extracellular matrix (ECM) receptor interactions that play a role in EMT induction in prostate cancer cells [64, 101]. …”

Section: Micrornas and Emt In Prostate Cancermentioning

confidence: 99%

MicroRNAs and epithelial-mesenchymal transition in prostate cancer

et al. 2016

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Prostate cancer (PCa) is a leading cause of male cancer-related deaths. A significant fraction of prostate tumors are very aggressive, often metastasizing to bone, causing significant morbidity and mortality. Also, PCa is associated with high rates of recurrence, often attributed to the existence of cancer stem cells. Epithelial-mesenchymal transition (EMT), a process characterized by decreased expression of epithelial genes and increased expression of mesenchymal genes, plays a critical role in tumor invasion, metastasis and recurrence. In PCa, EMT has been implicated particularly in the context of metastatic disease and microRNAs have emerged as critical post-transcriptional regulators of PCa EMT. In this review, we summarize the role of miRNAs in PCa EMT that play a role in progression, metastasis and recurrence. Studies till date suggest that microRNAs mediate efficient and reversible control of PCa EMT via multiple mechanisms including either by (i) directly repressing single or multiple EMT-TFs or regulating cytoskeletal components (epithelial/mesenchymal genes) or (ii) regulating key signaling pathways involved in EMT. Oncogenic microRNAs often act as EMT promoters by repressing epithelial characteristics and tumor suppressive miRNAs act by inhibiting mesenchymal progression. Further, EMT is mechanistically linked to stem cell signatures in PCa and several miRNAs implicated in EMT have been reported to influence PCa stem cells. Loss of EMT-inhibiting miRNAs and/or gain of EMT promoting miRNAs lead to induction of PCa EMT, leading to tumor progression, metastasis and recurrence. Restoring expression of tumor suppressive miRNAs and inhibiting oncogenic miRNAs represent potential therapeutic opportunities to prevent disease metastasis and recurrence.

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Twist induces epithelial-mesenchymal transition and cell motility in breast cancer via ITGB1-FAK/ILK signaling axis and its associated downstream network

Cited by 80 publications

References 48 publications

Interplay between intergrin-linked kinase and ribonuclease inhibitor affects growth and metastasis of bladder cancer through signaling ILK pathways

Interplay between intergrin-linked kinase and ribonuclease inhibitor affects growth and metastasis of bladder cancer through signaling ILK pathways

Advancement of mass spectrometry-based proteomics technologies to explore triple negative breast cancer

MicroRNAs and epithelial-mesenchymal transition in prostate cancer

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