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https://www.readbyqxmd.com/read/28630480/pro-invasive-stimuli-and-the-interacting-protein-hsp70-favour-the-route-of-alpha-enolase-to-the-cell-surface
#1
Giovanni Perconti, Cristina Maranto, Daniele P Romancino, Patrizia Rubino, Salvatore Feo, Antonella Bongiovanni, Agata Giallongo
Cell surface expression of alpha-enolase, a glycolytic enzyme displaying moonlighting activities, has been shown to contribute to the motility and invasiveness of cancer cells through the protein non-enzymatic function of binding plasminogen and enhancing plasmin formation. Although a few recent records indicate the involvement of protein partners in the localization of alpha-enolase to the plasma membrane, the cellular mechanisms underlying surface exposure remain largely elusive. Searching for novel interactors and signalling pathways, we used low-metastatic breast cancer cells, a doxorubicin-resistant counterpart and a non-tumourigenic mammary epithelial cell line...
June 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28627586/hsp70-acetylation-prevents-caspase-dependent-independent-apoptosis-and-autophagic-cell-death-in-cancer-cells
#2
Yoo Hoi Park, Ji Hae Seo, Ji-Hyeon Park, Hye Shin Lee, Kyu-Won Kim
Cancer cells are continuously challenged by adverse environmental factors including hypoxia, metabolite restriction, and immune reactions, and must adopt diverse strategies to survive. Heat shock protein (Hsp) 70 plays a central role in protection against stress-induced cell death by maintaining protein homeostasis and interfering with the process of programmed cell death. Recent findings have suggested that Hsp70 acetylation is a key regulatory modification required for its chaperone activity, but its relevance in the process of programmed cell death and the underlying mechanisms involved are not well understood...
June 12, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28617974/high-expression-of-heat-shock-proteins-and-heat-shock-factor-1-distinguishes-an-aggressive-subset-of-clear-cell-renal-cell-carcinoma
#3
Pao-Shu Wu, Yen-Hwa Chang, Chin-Chen Pan
AIMS: Heat shock proteins (HSPs) are a group of molecules induced by a variety of environmental and pathophysiologic stresses, including cancer. HSPs are implicated in the regulation of apoptosis and immunity in neoplasm. Transcription factor heat shock factor1 (HSF1) acts as the master regulator to control HSP expression, and therefore is involved in tumorigenesis. The purpose of this study was to evaluate the expression and clinicopathologic relevance of HSPs and HSF1 in clear cell renal cell carcinoma (ccRCC)...
June 15, 2017: Histopathology
https://www.readbyqxmd.com/read/28611991/substrate-discrimination-by-clpb-and-hsp104
#4
Danielle M Johnston, Marika Miot, Joel R Hoskins, Sue Wickner, Shannon M Doyle
ClpB of E. coli and yeast Hsp104 are homologous molecular chaperones and members of the AAA+ (ATPases Associated with various cellular Activities) superfamily of ATPases. They are required for thermotolerance and function in disaggregation and reactivation of aggregated proteins that form during severe stress conditions. ClpB and Hsp104 collaborate with the DnaK or Hsp70 chaperone system, respectively, to dissolve protein aggregates both in vivo and in vitro. In yeast, the propagation of prions depends upon Hsp104...
2017: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/28608409/neoadjuvant-chemoradiotherapy-of-pancreatic-cancer-induces-a-favorable-immunogenic-tumor-microenvironment-associated-with-increased-major-histocompatibility-complex-class-i-related-chain-a-b-expression
#5
Takashi Murakami, Yuki Homma, Ryusei Matsuyama, Ryutaro Mori, Kentaro Miyake, Yusaku Tanaka, Kanechika Den, Yoji Nagashima, Masatoshi Nakazawa, Yukihiko Hiroshima, Michio Ueda, Kuniya Tanaka, Robert M Hoffman, Michael Bouvet, Itaru Endo
BACKGROUND: Damage-associated molecular patterns (DAMPs) are related to immune responses in malignant tumors including tumor-infiltrating lymphocytes (TILs). The aim of the present study was to determine the relationship between expression of components of DAMPs and TILs in pancreatic cancer patients who underwent neoadjuvant chemoradiotherapy (NACRT) versus those who did not. METHODS: NACRT was administered to 51 patients with borderline-resectable pancreatic cancer and not to 33 patients with resectable pancreatic cancer...
June 12, 2017: Journal of Surgical Oncology
https://www.readbyqxmd.com/read/28593150/the-antitumor-effect-of-c-terminus-of-hsp70-interacting-protein-via-degradation-of-c-met-in-small-cell-lung-cancer
#6
Sung Ho Cho, Jong In Kim, Hyun Su Kim, Sung Dal Park, Kang Won Jang
BACKGROUND: The mesenchymal-epithelial transition factor (MET) receptor can be overexpressed in solid tumors, including small cell lung cancer (SCLC). However, the molecular mechanism regulating MET stability and turnover in SCLC remains undefined. One potential mechanism of MET regulation involves the C-terminus of Hsp70-interacting protein (CHIP), which targets heat shock protein 90-interacting proteins for ubiquitination and proteasomal degradation. In the present study, we investigated the functional effects of CHIP expression on MET regulation and the control of SCLC cell apoptosis and invasion...
June 2017: Korean Journal of Thoracic and Cardiovascular Surgery
https://www.readbyqxmd.com/read/28574736/multiple-functions-of-the-e3-ubiquitin-ligase-chip-in-immunity
#7
Shaohua Zhan, Tianxiao Wang, Wei Ge
The carboxyl terminal of Hsp70-interacting protein (CHIP) is an E3 ubiquitin ligase that plays a pivotal role in the protein quality control system by shifting the balance of the folding-refolding machinery toward the degradative pathway. However, the precise mechanisms by which nonnative proteins are selected for degradation by CHIP either directly or indirectly via chaperone Hsp70 or Hsp90 are still not clear. In this review, we aim to provide a comprehensive model of the mechanism by which CHIP degrades its substrate in a chaperone-dependent or direct manner...
June 2, 2017: International Reviews of Immunology
https://www.readbyqxmd.com/read/28569777/the-novel-hypoxia-inducible-factor-1%C3%AE-inhibitor-idf-11774-regulates-cancer-metabolism-thereby-suppressing-tumor-growth
#8
Hyun Seung Ban, Bo-Kyung Kim, Hongsub Lee, Hwan Mook Kim, Dipesh Harmalkar, Miso Nam, Song-Kyu Park, Kiho Lee, Joon-Tae Park, Inhyub Kim, Kyeong Lee, Geum-Sook Hwang, Misun Won
HIF-1 is associated with poor prognoses and therapeutic resistance in cancer patients. We previously developed a novel hypoxia-inducible factor (HIF)-1 inhibitor, IDF-11774, a clinical candidate for cancer therapy. We also reported that IDF-1174 inhibited HSP70 chaperone activity and suppressed accumulation of HIF-1α. In this study, IDF-11774 inhibited the accumulation of HIF-1α in vitro and in vivo in colorectal carcinoma HCT116 cells under hypoxic conditions. Moreover, IDF-11774 treatment suppressed angiogenesis of cancer cells by reducing the expression of HIF-1 target genes, reduced glucose uptake, thereby sensitizing cells to growth under low glucose conditions, and decreased the extracellular acidification rate (ECAR) and oxygen consumption rate of cancer cells...
June 1, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28567003/evidence-of-a-cell-surface-role-for-hsp90-complex-proteins-mediating-neuroblast-migration-in-the-subventricular-zone
#9
Leo M Miyakoshi, Diego Marques-Coelho, Luiz E R De Souza, Flavia R S Lima, Vilma R Martins, Silvio M Zanata, Cecilia Hedin-Pereira
In most mammalian brains, the subventricular zone (SVZ) is a germinative layer that maintains neurogenic activity throughout adulthood. Neuronal precursors arising from this region migrate through the rostral migratory stream (RMS) and reach the olfactory bulbs where they differentiate and integrate into the local circuitry. Recently, studies have shown that heat shock proteins have an important role in cancer cell migration and blocking Hsp90 function was shown to hinder cell migration in the developing cerebellum...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28543919/-heat-shock-protein-70-in-pancreatic-diseases-friend-or-foe
#10
REVIEW
Bhuwan Giri, Vrishketan Sethi, Shrey Modi, Bharti Garg, Sulagna Banerjee, Ashok Saluja, Vikas Dudeja
The heat shock response in pancreatitis that is activated via HSP70 protects acinar cells through multiple simultaneous mechanisms. It inhibits trypsinogen activation and modulates NF-κB signaling to limit acinar cell injury. On the other hand, HSP70 is overexpressed in pancreatic cancer and is hijacked by the cellular machinery to inhibit apoptosis. Inhibition of HSP70 in pancreatic cancer by a novel compound, Minnelide, has shown considerable clinical promise.
May 22, 2017: Journal of Surgical Oncology
https://www.readbyqxmd.com/read/28542269/the-small-molecule-kinase-inhibitor-d11-counteracts-17-aag-mediated-up-regulation-of-hsp70-in-brain-cancer-cells
#11
Susanne Schaefer, Tina H Svenstrup, Barbara Guerra
Many types of cancer express high levels of heat shock proteins (HSPs) that are molecular chaperones regulating protein folding and stability ensuring protection of cells from potentially lethal stress. HSPs in cancer cells promote survival, growth and spreading even in situations of growth factors deprivation by associating with oncogenic proteins responsible for cell transformation. Hence, it is not surprising that the identification of potent inhibitors of HSPs, notably HSP90, has been the primary research focus, in recent years...
2017: PloS One
https://www.readbyqxmd.com/read/28536268/endoplasmic-reticulum-stress-induced-degradation-of-dnajb12-stimulates-bok-accumulation-and-primes-cancer-cells-for-apoptosis
#12
Pattarawut Sopha, Hong Yu Ren, Diane E Grove, Douglas M Cyr
DNAJB12 (JB12) is an endoplasmic reticulum (ER)-associated Hsp40 family protein that recruits Hsp70 to the ER surface to coordinate the function of ER-associated and cytosolic chaperone systems in protein quality control. Hsp70 is stress inducible, but paradoxically, we report here that JB12 was degraded by the proteasome during severe ER stress. Destabilized JB12 was degraded by ER-associated degradation (ERAD) complexes that contained HERP, Sel1L, and gp78. JB12 was the only ER-associated chaperone that was destabilized by reductive stress...
May 23, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28536143/aurora-kinase-a-promotes-ar-degradation-via-the-e3-ligase-chip
#13
Sukumar Sarkar, David L Brautigan, James M Larner
Reducing the levels of the androgen receptor (AR) is one of the most viable approaches to combat castration-resistant prostate cancer (CRPC). Previously, we observed that proteasomal-dependent degradation of AR in response to 2-methoxyestradiol (2-ME) depends primarily on the E3 ligase C-terminus of HSP70-interacting protein (STUB1/CHIP). Here, 2-ME stimulation activates CHIP by phosphorylation via Aurora kinase A (AURKA). Aurora A kinase inhibitors and RNAi knockdown of Aurora A transcript selectively blocked CHIP phosphorylation and AR degradation...
May 23, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28510570/bag-1-as-a-biomarker-in-early-breast-cancer-prognosis-a-systematic-review-with-meta-analyses
#14
E S Papadakis, T Reeves, N H Robson, T Maishman, G Packham, R I Cutress
BACKGROUND: The co-chaperone protein Bcl-2-associated athanogene-1 (BAG-1) is overexpressed in breast cancer and has been incorporated in the oncotype DX and PAM50 breast cancer prognostic assays. Bcl-2-associated athanogene-1 exists as multiple protein isoforms that interact with diverse partners, including chaperones Hsc70/Hsp70, Ser/Thr kinase Raf-1 and Bcl-2, to promote cancer cell survival. The BAG-1L isoform specifically binds to and increases the transcriptional activity of oestrogen receptor in cells, and in some, but not all studies, BAG-1 expression is predictive of clinical outcome in breast cancer...
June 6, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28504248/the-flavonoid-tl-2-8-induces-cell-death-and-immature-mitophagy-in-breast-cancer-cells-via-abrogating-the-function-of-the-aha1-hsp90-complex
#15
Hui-Juan Liu, Xiao-Xiao Jiang, Yi-Zhen Guo, Fang-Hui Sun, Xin-Hui Kou, Yong Bao, Zhu-Qing Zhang, Zhao-Hu Lin, Ting-Bo Ding, Lan Jiang, Xin-Sheng Lei, Yong-Hua Yang
The flavonoid quercetin exhibits significant anticancer activities with few side effects. In the current study, we characterized TL-2-8, a quercetin derivative, as a novel anticancer agent in vitro and in vivo. Cell proliferation and viability were assessed using Cell Counting Kit-8 and CellTiter-Blue assay, respectively. Cell death was examined using PI staining or a TUNEL assay. Mitophagy was determined by measuring autophagic flux and by confocal imaging. Protein expression was examined by Western blotting...
May 1, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28486965/site-specific-gene-expression-patterns-in-oral-cancer
#16
Gesche Frohwitter, Horst Buerger, Eberhard Korsching, Paul J van Diest, Johannes Kleinheinz, Thomas Fillies
BACKGROUND: Squamous cell carcinomas (SCCs) are the most prevalent malignant tumours within the head and neck. Evidence exists that distinct genes are differentially regulated in SCCs of the oral cavity compared to other head and neck regions. Given this background, the aim of this study was to investigate whether such tumour site-specific gene expression can also be observed in different localizations within the oral cavity. METHODS: Using tissue microarrays (TMAs), we investigated 76 SCCs of the floor of the mouth, 49 SCCs of the tongue and 68 SCCs of other anatomic regions within the oral cavity...
May 10, 2017: Head & Face Medicine
https://www.readbyqxmd.com/read/28484090/inhibition-of-stress-inducible-hsp70-impairs-mitochondrial-proteostasis-and-function
#17
Julia I-Ju Leu, Thibaut Barnoud, Gao Zhang, Tian Tian, Zhi Wei, Meenhard Herlyn, Maureen E Murphy, Donna L George
Protein quality control is an important component of survival for all cells. The use of proteasome inhibitors for cancer therapy derives from the fact that tumor cells generally exhibit greater levels of proteotoxic stress than do normal cells, and thus cancer cells tend to be more sensitive to proteasome inhibition. However, this approach has been limited in some cases by toxicity to normal cells. Recently, the concept of inhibiting proteostasis in organelles for cancer therapy has been advanced, in part because it is predicted to have reduced toxicity for normal cells...
April 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28466152/suppression-of-heat-shock-protein-70-by-sirna-enhances-the-antitumor-effects-of-cisplatin-in-cultured-human-osteosarcoma-cells
#18
Yuki Mori, Ryu Terauchi, Toshiharu Shirai, Shinji Tsuchida, Naoki Mizoshiri, Yuji Arai, Tsunao Kishida, Hiroyoshi Fujiwara, Osam Mazda, Toshikazu Kubo
Although advances in chemotherapy have improved the prognosis for osteosarcoma, some patients do not respond sufficiently to treatment. Heat shock protein 70 (Hsp70) is expressed at high levels in cancer cells and attenuates the therapeutic efficacy of anticancer agents, resulting in a poorer prognosis. This study investigated whether small interfering RNA (siRNA)-mediated inhibition of Hsp70 expression in an osteosarcoma cell line would enhance sensitivity to cisplatin. The expression of Hsp70 with cisplatin treatment was observed by using Western blotting and real-time reverse transcription polymerase chain reaction (RT-PCR)...
May 2, 2017: Cell Stress & Chaperones
https://www.readbyqxmd.com/read/28464914/efficacy-of-radiotherapy-for-the-treatment-of-cystic-echinococcosis-in-naturally-infected-sheep
#19
Rui Mao, Wen-Bao Zhang, Hong-Zhi Qi, Tao Jiang, Ge Wu, Peng-Fei Lu, Abudula Ainiwaer, Ge Shang, Lin Xu, Jie Hao, Xi Shou, Hai-Tao Li, Jun Li, Song-An Zhang, Yong-Xing Bao, Hao Wen
BACKGROUND: Radiotherapy is commonly used to treat cancers. To date, there has been no study focusing on the effects of radiotherapy on hydatid disease in large animals. In this study, we aim to investigate the efficiency and safety of radiotherapy for treating hydatid disease caused by Echinococcus granulosus in naturally infected sheep. METHODS: Ultrasound was used to screen naturally infected sheep in an echinococcosis endemic area in Xinjiang, China. A computer tomography (CT) scan confirmed the presence of hydatid cysts...
May 3, 2017: Infectious Diseases of Poverty
https://www.readbyqxmd.com/read/28458133/scutellarin-derivatives-as-apoptosis-inducers-design-synthesis-and-biological-evaluation
#20
Tong Han, Jia Li, Jingjing Xue, He Li, Fanxing Xu, Keguang Cheng, Dahong Li, Zhanlin Li, Ming Gao, Huiming Hua
To explore novel antitumor agents with high efficiency and low toxicity, a series of NO-donating scutellarin derivatives (14-17) were synthesized and the antiproliferative activities against MCF-7, HCT-116, PC-3 and HepG2 cancer cell lines were assessed. Among them, compound 14b was the strongest with IC50 values of 2.96 μM, 7.25 μM, 0.09 μM and 0.50 μM, respectively, and displayed low toxicity against normal human liver L-O2 cells with an IC50 of 47.96 μM, showing good selectivity between normal and malignant liver cells...
April 21, 2017: European Journal of Medicinal Chemistry
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