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Role of CCL20 mediated immune cell recruitment in NF- κB mediated TRAIL resistance of pancreatic cancer
In conclusion, our data show a functional role of a RelA-CCL20 pathway in PDAC TRAIL resistance. We demonstrate how the therapy-induced cross-talk of cancer cells with immune cells affects treatment responses, knowledge needed to tailor novel bi-specific treatments, which target tumor cell as well as immune cells. Graphical abstract
Source: Biochimica et Biophysica Acta (BBA) Molecular Cell Research - February 7, 2017 Category: Molecular Biology Source Type: research

Crosstalk between different family members: IL27 recapitulates IFN γ responses in HCC cells, but is inhibited by IL6-type cytokines
In this study, we show that IL27 induces STAT1 and STAT3 phosphorylation in 5 HCC lines and 3 different types of non-transformed liver cells. We were especially interested in the relevance of the IL27-induced STAT3 activation in liver cells. Thus, we compared the IL27 responses with those induced by IFNγ (STAT1-dominated response) or IL6-type cytokines (IL6, hyper-IL6 (hy-IL6) or OSM) (STAT3-dominated response) by microarray analysis and find that in HCC cells, IL27 induces an IFNγ-like, STAT1-dependent transcriptional response, but we do not find an effective STAT3-dependent response. Validation experiments corroborate ...
Source: Biochimica et Biophysica Acta (BBA) Molecular Cell Research - December 9, 2016 Category: Molecular Biology Source Type: research

Interaction with epsin 1 regulates the constitutive clathrin-dependent internalization of ErbB3
Conclusion Altogether the results are consistent with a model whereby both constitutive and ligand-induced internalization of ErbB3 are regulated through interaction with epsin 1. General significance Internalization is an important regulator of growth factor receptor mediated signaling and the current study identify mechanisms regulating plasma membrane turnover of ErbB3. Graphical abstract
Source: Biochimica et Biophysica Acta (BBA) Molecular Cell Research - March 11, 2016 Category: Molecular Biology Source Type: research

Leukotriene B4 receptor-2 contributes to chemoresistance of SK-OV-3 ovarian cancer cells through activation of signal transducer and activator of transcription-3-linked cascade
In this study, we found that the low-affinity leukotriene B4 receptor-2 (BLT2) and its ligand leukotriene B4 were highly up-regulated in cisplatin-resistant SK-OV-3 ovarian cancer cells and play critical roles in mediating the chemoresistance through the activation of signal transducer and activator of transcription-3 (STAT-3) and the subsequent up-regulation of interleukin-6 (IL-6). BLT2 depletion with siRNA clearly abolished the chemoresistance to cisplatin in SK-OV-3 ovarian cancer cells and further increased cell sensitivity to cisplatin chemotherapy by down-regulating the ‘STAT-3-IL-6’ cascade. Enlarged tumor form...
Source: Biochimica et Biophysica Acta (BBA) Molecular Cell Research - November 22, 2015 Category: Molecular Biology Source Type: research

Cross-talk between lysophosphatidic acid receptor 1 and tropomyosin receptor kinase a promotes lung epithelial cell migration
Publication date: Available online 17 November 2015 Source:Biochimica et Biophysica Acta (BBA) - Molecular Cell Research Author(s): Ling Nan, Jianxin Wei, Anastasia M. Jacko, Miranda K. Culley, Jing Zhao, Viswanathan Natarajan, Haichun Ma, Yutong Zhao Lysophosphatidic acid (LPA) is a bioactive lysophospholipid, which plays a crucial role in regulation of cell proliferation, migration, and differentiation. LPA exerts its biological effects mainly through binding to cell-surface LPA receptors (LPA1-6), which belong to the G protein-coupled receptor (GPCR) family. Recent studies suggest that cross-talk between recep...
Source: Biochimica et Biophysica Acta (BBA) Molecular Cell Research - November 22, 2015 Category: Molecular Biology Source Type: research

TRPV6 channel modulates proliferation of insulin secreting INS-1E beta cell line
In conclusion, this study demonstrates for the first time the expression of TRPV6 in INS-1E cells and rat pancreatic beta cells and describes its role in modulating calcium signaling, beta cell proliferation and insulin mRNA expression. In contrast, TRPV6 fails to influence insulin secretion.
Source: Biochimica et Biophysica Acta (BBA) Molecular Cell Research - October 5, 2015 Category: Molecular Biology Source Type: research

Tensin1 positively regulates RhoA activity through its interaction with DLC1
Publication date: December 2015 Source:Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Volume 1853, Issue 12 Author(s): Yi-Ping Shih, Peng Sun, Aifeng Wang, Su Hao Lo DLC1 is a RhoGAP-containing tumor suppressor and many of DLC1's functions are absolutely dependent on its RhoGAP activity. Through its RhoGAP domain, DLC1 inhibits the activity of RhoA GTPase, which regulates actin cytoskeleton networks and dis/assembly of focal adhesions. Tensin1 (TNS1) is a focal adhesion molecule that links the actin cytoskeleton to integrins and forms signaling complexes through its multiple binding domains. Here, we ...
Source: Biochimica et Biophysica Acta (BBA) Molecular Cell Research - October 4, 2015 Category: Molecular Biology Source Type: research

Mitochondrial DNA has a pro-inflammatory role in AMD
This study contributes to our understanding of the potential pro-inflammatory role of mtDNA in the pathogenesis of AMD. Graphical abstract
Source: Biochimica et Biophysica Acta (BBA) Molecular Cell Research - September 7, 2015 Category: Molecular Biology Source Type: research

Dominant negative Ras attenuates pathological ventricular remodeling in pressure overload cardiac hypertrophy
We examined the possible anti-hypertrophic effect of Ras inhibition in vitro using rat neonatal cardiomyocytes (NRCM) and in vivo in the setting of pressure-overload left ventricular (LV) hypertrophy (POH) in rats. Ras functions were modulated via adenovirus directed gene transfer of active mutant Ras-Val12 or dominant negative mutant N17-DN-Ras (DN-Ras). Ras-Val12 expression in vitro activates NFAT resulting in pro-hypertrophic and cardio-toxic effects on NRCM beating and Z-line organization. In contrast, the DN-Ras was antihypertrophic on NRCM, inhibited NFAT and exerted cardio-protective effects attested by preserved NR...
Source: Biochimica et Biophysica Acta (BBA) Molecular Cell Research - September 4, 2015 Category: Molecular Biology Source Type: research

Oncostatin M-dependent Mcl-1 induction mediated by JAK1/2-STAT1/3 and CREB contributes to bioenergetic improvements and protective effects against mitochondrial dysfunction in cortical neurons
In conclusion, our findings indicated that OSM induces Mcl-1 expression via activation of ERK1/2, JAK1/2, STAT1/3, and CREB; furthermore, OSM-mediated Mcl-1 induction contributes to bioenergetic improvements and neuroprotective effects against 3-NP toxicity in cortical neurons. OSM may thus serve as a novel neuroprotective agent against mitochondrial dysfunction commonly associated with pathogenic mechanisms underlying neurodegeneration.
Source: Biochimica et Biophysica Acta (BBA) Molecular Cell Research - May 16, 2015 Category: Molecular Biology Source Type: research

Nuclear envelope proteins Nesprin2 and LaminA regulate proliferation and apoptosis of vascular endothelial cells in response to shear stress
Publication date: Available online 23 February 2015 Source:Biochimica et Biophysica Acta (BBA) - Molecular Cell Research Author(s): Yue Han , Lu Wang , Qing-Ping Yao , Ping Zhang , Bo Liu , Guo-Liang Wang , Bao-Rong Shen , Binbin Cheng , Yingxiao Wang , Zong-Lai Jiang , Ying-Xin Qi The dysfunction of vascular endothelial cells (ECs) influenced by flow shear stress is crucial for vascular remodeling. However, the roles of nuclear envelope (NE) proteins in shear stress-induced EC dysfunction are still unknown. Our results indicated that, compared with normal shear stress (NSS), low shear stress (LowSS) suppressed the expre...
Source: Biochimica et Biophysica Acta (BBA) Molecular Cell Research - February 23, 2015 Category: Molecular Biology Source Type: research

Mitochondrial function contributes to oxysterol-induced osteogenic differentiation in mouse embryonic stem cells
This study investigated the effect of an oxysterol combination of 22(S)-hydroxycholesterol and 20(S)-hydroxycholesterol (SS) on osteogenic differentiation of ESCs and the alterations to mitochondrial activity during differentiation. Osteogenic differentiation was assessed by alkaline phosphatase (ALP) activity, matrix mineralization, mRNA expression of osteogenic factors, runt-related transcription factor 2, osterix, and osteocalcin, and protein levels of collagen type IA (COLIA) and osteopontin (OPN). Treatment of cells with SS increased osteoinductive activity compared to the control group. Intracellular reactive oxygen ...
Source: Biochimica et Biophysica Acta (BBA) Molecular Cell Research - January 24, 2015 Category: Molecular Biology Source Type: research

Mitochondrial function contributes to oxysterols-induced osteogenic differentiation in mouse embryonic stem cells
This study investigated the effect of an oxysterol combination of 22(S)-hydroxycholesterol and 20(S)-hydroxycholesterol (SS) on osteogenic differentiation of ESCs and the alterations to mitochondrial activity during differentiation. Osteogenic differentiation was assessed by alkaline phosphatase (ALP) activity, matrix mineralization, mRNA expression of osteogenic factors, runt-related transcription factor 2, osterix, and osteocalcin, and protein levels of collagen type IA (COLIA) and osteopontin (OPN). Treatment of cells with SS increased osteoinductive activity compared to the control group. Intracellular reactive oxygen ...
Source: Biochimica et Biophysica Acta (BBA) Molecular Cell Research - December 16, 2014 Category: Molecular Biology Source Type: research

Downregulation of diacylglycerol kinase ζ enhances activation of cytokine-induced NF-κB signaling pathway
This study shows that siRNA-mediated DGKζ knockdown in HeLa cells facilitates degradation of IκB, followed by nuclear translocation of NF-κB p65 subunit. In addition, DGKζ-deficient MEFs show upregulation of p65 subunit phosphorylation at Serine 468 and 536 and its interaction with CBP transcriptional coactivator upon TNF-α stimulation. These modifications of p65 subunit might engender enhanced NF-κB transcriptional reporter assay of DGKζ knockdown cells. These findings provide further insight into the regulatory mechanisms of cytokine-induced NF-κB activation.
Source: Biochimica et Biophysica Acta (BBA) Molecular Cell Research - December 5, 2014 Category: Molecular Biology Source Type: research

CSN-associated USP48 confers stability to nuclear NF-κB/RelA by trimming K48-linked Ub-chains
In this study we observed that USP48, a DUB of hitherto ill-defined function identified through a siRNA screen, associates with the CSN and RelA in the nucleus. We show that USP48 trims rather than completely disassembles long K48-linked free and substrate-anchored Ub-chains, a catalytic property only shared with ataxin-3 (Atx3) and otubain-1 (OTU1), and that USP48 Ub-chain-trimming activity is regulated by casein-kinase-2 (CK2)-mediated phosphorylation in response to cytokine-stimulation. Functionally, we demonstrate for the first time the CSN and USP48 to cooperatively stabilize the nuclear pool of RelA, thereby facilita...
Source: Biochimica et Biophysica Acta (BBA) Molecular Cell Research - December 5, 2014 Category: Molecular Biology Source Type: research

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