Targeting Interleukin-11 Receptor-α Impairs Human Endometrial Cancer Cell Proliferation and Invasion <i>In Vitro</i> and Reduces Tumor Growth and Metastasis <i>In Vivo</i>

Winship, Amy; Sinderen, Michelle Van; Donoghue, Jacqueline F.; Rainczuk, Kate; Dimitriadis, Evdokia

doi:10.1158/1535-7163.mct-15-0677

Cited by 40 publications

(44 citation statements)

References 46 publications

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“…High IL-11Rα chain expression is an independent predictor in renal cell carcinoma43. IL-11Rα may also be a target for treatment of endometrial cancer44 and prostate cancer45. In our study, we did not detect any change of the expression of IL-11Rα in lung cancer cells by cisplatin.…”

Section: Discussioncontrasting

confidence: 53%

Cancer-associated fibroblasts treated with cisplatin facilitates chemoresistance of lung adenocarcinoma through IL-11/IL-11R/STAT3 signaling pathway

Tao

Huang

Wang

et al. 2016

Sci Rep

101

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Cancer-associated fibroblasts (CAF) are recognized as one of the key determinants in the malignant progression of lung adenocarcinoma. And its contributions to chemoresistance acquisition of lung cancer has raised more and more attention. In our study, cancer associated fibroblasts treated with cisplatin conferred chemoresistance to lung cancer cells. Meanwhile, Interleukin-11(IL-11) was significantly up-regulated in the CAF stimulated by cisplatin. As confirmed in lung adenocarcinoma cells in vivo and in vitro, IL-11 could protect cancer cells from cisplatin-induced apoptosis and thus promote their chemoresistance. Furthermore, it was also observed that IL-11 induced STAT3 phosphorylation and increased anti-apoptotic protein Bcl-2 and Survivin expression in cancer cells. The effect could be abrogated by suppressing STAT3 phosphorylation or silencing IL-11Rα expression in cancer cells. In conclusion, chemotherapy-induced IL-11 upregulation in CAF promotes lung adenocarcinoma cell chemoresistance by activating IL-11R/STAT3 anti-apoptotic signaling pathway.

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Section: Discussioncontrasting

confidence: 53%

Cancer-associated fibroblasts treated with cisplatin facilitates chemoresistance of lung adenocarcinoma through IL-11/IL-11R/STAT3 signaling pathway

Tao

Huang

Wang

et al. 2016

Sci Rep

101

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“…xCELLigence (ACEA Biosciences, USA) is an example of a commercially available platform with ECIS technique (Hong, Kandasamy, Marimuthu, Choi, & Kim, 2011). Winship, Van Sinderen, Donoghue, Rainczuk, and Dimitriadis (2016) have used the commercially available platform xCELLigence to monitor the effects of interleukin 11, a cytokine, on endometrial epithelial cancer (G1-3) cell proliferation. E-Plates are special type of plates (16 or 96) used to measure cell proliferation in electrical impedance assays.…”

Section: Electric Cell-substrate Impedance Sensingmentioning

confidence: 99%

In vitro assays and techniques utilized in anticancer drug discovery

Ediriweera

Tennekoon

Samarakoon

2018

J of Applied Toxicology

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Development of a cancer is a multistep process and six major hallmarks of cancer that are known to control malignant transformation have been described. Anticancer drug development is a tedious process, requiring a number of in vitro, in vivo and clinical studies. In vitro assays provide an initial platform for cancer drug discovery approaches. A wide range of in vitro assays/techniques have been developed to evaluate each hallmark feature of cancer and selection of a particular in vitro assay or technique mainly depends on the specific research question (s) to be examined. In the present review, we have described some commonly utilized in vitro assays and techniques used to examine cell viability/proliferation, apoptosis, cellular senescence, invasion and migration, oxidative stress and antioxidant effects, gene and protein expression, angiogenesis and genomic alterations in cancer drug discovery. Additionally, uses of modern techniques such as high throughput screening, high content screening and reporter gene assays in cancer drug discovery have also been described.

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“…IL-11 is elevated in endometrial tumors and uterine lavage fluid in women with endometrial cancer, altering endometrial epithelial cancer cell adhesion and migration in vitro. Targeted blockade of endometrial cancer epithelial cell IL-11 signaling reduces primary tumor growth and impaired metastasis in ectopic and orthotopic endometrial cancer models in vivo [94].…”

Section: Il-11 Functionsmentioning

confidence: 99%

Interleukin-11: A Multifunctional Cytokine with Intrinsically Disordered Regions

Permyakov

Uversky

Permyakov

2016

Cell Biochem Biophys

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Cytokine interleukin-11 (IL-11) is a multifunctional protein with diverse roles in the normal cell signaling and in various pathologies. The structure of IL-11 is characterized by a four-helix bundle motif comprising two pairs of antiparallel α-helices arranged in an up-up-down-down configuration. Evaluation of the intrinsic disorder predisposition of human IL-11 by several computational tools clearly shows that this protein is predicted to have functional disordered regions potentially involved in interaction with natural binding partners. Signaling by IL-11 proceeds via an interaction of the protein with its membrane-specific receptor IL-11Rα and a subsequent interaction of the complex with the transmembrane signal-transducing receptor GP130. Cytoplasmic domain of IL-11Rα is predicted to be very disordered, and noticeable amount of disorder is present even in the large extracellular domain of the protein. GP130 is also predicted to have long disordered region that is located at the C-terminal of the protein and is expected to have several disorder-based binding sites. It shows that intrinsic disorder might play an important role in functioning of this signaling machine. A specific subset of the calcium sensor proteins (calmodulin, S100P, S100B, NCS-1, GCAP-1/2) exhibits metal-dependent binding of IL-11 with dissociation constants in a range of 1-19 μM, and the structural features of their hinge regions likely ensure selectivity and calcium sensitivity of IL-11 binding to the EF-hand proteins studied. IL-11 exhibits multiple effects on hematopoietic and non-hematopoietic systems. It plays a major role in orchestrating complex processes of tumor development and progression.

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Targeting Interleukin-11 Receptor-α Impairs Human Endometrial Cancer Cell Proliferation and Invasion In Vitro and Reduces Tumor Growth and Metastasis In Vivo

Cited by 40 publications

References 46 publications

Cancer-associated fibroblasts treated with cisplatin facilitates chemoresistance of lung adenocarcinoma through IL-11/IL-11R/STAT3 signaling pathway

Cancer-associated fibroblasts treated with cisplatin facilitates chemoresistance of lung adenocarcinoma through IL-11/IL-11R/STAT3 signaling pathway

In vitro assays and techniques utilized in anticancer drug discovery

Interleukin-11: A Multifunctional Cytokine with Intrinsically Disordered Regions

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