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Mitotic cell death

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https://www.readbyqxmd.com/read/28644436/the-lats1-and-lats2-tumor-suppressors-beyond-the-hippo-pathway
#1
REVIEW
Noa Furth, Yael Aylon
Proper cellular functionality and homeostasis are maintained by the convergent integration of various signaling cascades, which enable cells to respond to internal and external changes. The Dbf2-related kinases LATS1 and LATS2 (LATS) have emerged as central regulators of cell fate, by modulating the functions of numerous oncogenic or tumor suppressive effectors, including the canonical Hippo effectors YAP/TAZ, the Aurora mitotic kinase family, estrogen signaling and the tumor suppressive transcription factor p53...
June 23, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28643424/mdm2-is-implicated-in-high-glucose-induced-podocyte-mitotic-catastrophe-via-notch1-signalling
#2
Hui Tang, Chun-Tao Lei, Chen Ye, Pan Gao, Cheng Wan, Shan Chen, Fang-Fang He, Yu-Mei Wang, Hua Su, Chun Zhang
Podocyte injury and depletion are essential events involved in the pathogenesis of diabetic nephropathy (DN). As a terminally differentiated cell, podocyte is restricted in 'post-mitosis' state and unable to regenerate. Re-entering mitotic phase will cause podocyte disastrous death which is defined as mitotic catastrophe (MC). Murine double minute 2 (MDM2), a cell cycle regulator, is widely expressed in renal resident cells including podocytes. Here, we explore whether MDM2 is involved in podocyte MC during hyperglycaemia...
June 23, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28638459/towards-prognostic-profiling-of-non-small-cell-lung-cancer-new-perspectives-on-the-relevance-of-polo-like-kinase-1-expression-the-tp53-mutation-status-and-hypoxia
#3
Jolien Van den Bossche, Christophe Deben, Ken Op de Beeck, Vanessa Deschoolmeester, Christophe Hermans, Ines De Pauw, Julie Jacobs, Paul Van Schil, Jan Baptist Vermorken, Patrick Pauwels, Marc Peeters, Filip Lardon, An Wouters
Background: Currently, prognosis of non-small cell lung cancer (NSCLC) patients is based on clinicopathological factors, including TNM stage. However, there are considerable differences in patient outcome within a similar staging group, even when patients received identical treatments. In order to improve prognostic predictions and to guide treatment options, additional parameters influencing outcome are required. Polo-like kinase 1 (Plk1), a master regulator of mitotic cell division and the DNA damage response, is considered as a new potential biomarker in this research area...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28637720/notch1-maintains-dormancy-of-olfactory-horizontal-basal-cells-a-reserve-neural-stem-cell
#4
Daniel B Herrick, Brian Lin, Jesse Peterson, Nikolai Schnittke, James E Schwob
The remarkable capacity of the adult olfactory epithelium (OE) to regenerate fully both neurosensory and nonneuronal cell types after severe epithelial injury depends on life-long persistence of two stem cell populations: the horizontal basal cells (HBCs), which are quiescent and held in reserve, and mitotically active globose basal cells. It has recently been demonstrated that down-regulation of the ΔN form of the transcription factor p63 is both necessary and sufficient to release HBCs from dormancy. However, the mechanisms by which p63 is down-regulated after acute OE injury remain unknown...
June 21, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28634860/molecular-chaperone-hsp70-and-its-constitutively-active-form-hsc70-play-an-indispensable-role-during-eye-development-of-drosophila-melanogaster
#5
Ajay Kumar, Anand K Tiwari
In the present study, we demonstrate that molecular chaperone Hsp70 and Hsc70 is essential for normal organization and development of ommatidial cells in Drosophila melanogaster eye. An exogenously expressed dominant negative mutant of Hsp70 (K71E) and Hsc70.4 (K71S and D206S) in an eye-specific manner resulted in eye degeneration that includes loss of eye pigment, disorganized ommatidia, abnormality in bristle cell arrangement and reduction in the eye size. The developmental organization of ommatidial cells (cone, photoreceptor, pigment, and bristle cell complex) was disturbed in Hsp70 and Hsc70 mutants...
June 20, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28622294/hepatocyte-nuclear-factor-1b-is-a-novel-negative-regulator-of-white-adipocyte-differentiation
#6
Xin Wang, Hao Wu, Weihua Yu, Jiangzheng Liu, Jie Peng, Nai Liao, Jieling Zhang, Xiaodi Zhang, Chunxu Hai
Hepatocyte nuclear factor 1b (HNF1b) is a transcription factor belonging to the HNF family. We aimed to investigate the role of HNF1b in white adipocyte differentiation. The expression of HNF1b was reduced in white adipose tissue (WAT) of both diet-induced and genetic obese mice and decreased during the process of 3T3-L1 adipocyte differentiation. Downregulation of HNF1b enhanced 3T3-L1 adipocyte differentiation and upregulation of HNF1b inhibited this process. Upregulation of HNF1b inhibited peroxisome proliferator-activated receptor γ (PPARγ) and its target gene expression, while downregulation of HNF1b increased those genes expression...
June 16, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28616577/caspase-2-in-mitotic-catastrophe-the-terminator-of-aneuploid-and-tetraploid-cells
#7
Ilio Vitale, Gwenola Manic, Maria Castedo, Guido Kroemer
Mitotic catastrophe is an oncosuppressive mechanism that targets cells experiencing defective mitoses via the activation of specific cell cycle checkpoints, regulated cell death pathways and/or cell senescence. This prevents the accumulation of karyotypic aberrations, which otherwise may drive oncogenesis and tumor progression. Here, we summarize experimental evidence confirming the role of caspase 2 (CASP2) as the main executor of mitotic catastrophe, and we discuss the signals that activate CASP2 in the presence of mitotic aberrations...
2017: Molecular & Cellular Oncology
https://www.readbyqxmd.com/read/28615297/disruption-of-aneuploidy-and-senescence-induced-by-aurora-inhibition-promotes-intrinsic-apoptosis-in-double-hit-or-double-expressor-diffuse-large-b-cell-lymphomas
#8
Daruka Mahadevan, Shariful Islam, Wenqing Qi, Carla Morales, Laurence Cooke, Catherine Spier, Eric Weterings
Double Hit (DH) or Double Expressor (DE) diffuse large B-cell lymphoma (DLBCL) are aggressive Non-Hodgkin's Lymphomas (NHLs) with translocations and/or over-expressions of MYC and BCL-2, that are difficult to treat. Aurora kinase (AK) inhibition with alisertib in DH/DE-DLBCL induces cell death in ~30%, while ~70% are aneuploid and senescent cells (AASCs), a mitotic escape mechanism contributing to drug resistance. These AASCs elaborated a high metabolic rate by increased AKT/mTOR and ERK/MAPK activity via BTK signaling through the chronic active B-cell receptor (BCR) pathway...
June 14, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28612617/-breast-cancer-in-young-women-correlation-of-clinical-histomorphological-and-molecular-genetic-features-of-breast-carcinoma-in-women-younger-than-35-years-of-age
#9
A Metelková, A Skálová, J Fínek
BACKGROUND: Worldwide, breast cancer is the leading type of malignancy in women. For premenopausal women, the disease brings much higher risk as it is usually more aggressive with worse prognosis. PATIENTS AND METHODS: In this retrospective study, 92 women treated at the Department of Oncology and Radiotherapy in Pilsen were selected from a basic cohort of 356 women under 35 years of age with breast cancer who were diagnosed between 2006 and 2015. The control group comprised 100 postmenopausal women over 65 years of age who were treated for invasive breast cancer...
2017: Klinická Onkologie: Casopis Ceské a Slovenské Onkologické Spolecnosti
https://www.readbyqxmd.com/read/28609167/hdr-brachytherapy-decreases-proliferation-rate-and-cellular-progression-of-a-radioresistant-human-squamous-cell-carcinoma-in-vitro
#10
Jony M Geraldo, Sérgio Scalzo, Daniela S Reis, Thiago L Leão, Silvia Guatimosim, Luiz O Ladeira, Lídia M Andrade
PURPOSE: To investigate the effects of HDR brachytherapy on cellular progression of a radioresistant human squamous cell carcinoma in vitro, based on clinical parameters. MATERIALS AND METHODS: An acrylic platform was designed to attach tissue culture flasks and assure source positioning during irradiation. At exponential phase, A431cells, a human squamous cell carcinoma, were irradiated two times up to 1100cGy. Cellular proliferation was assessed by Trypan blue exclusion assay and survival fraction was calculated by clonogenic assay...
June 13, 2017: International Journal of Radiation Biology
https://www.readbyqxmd.com/read/28603525/modulating-both-tumor-cell-death-and-innate-immunity-is-essential-for-improving-radiation-therapy-effectiveness
#11
REVIEW
Qiuji Wu, Awatef Allouch, Isabelle Martins, Catherine Brenner, Nazanine Modjtahedi, Eric Deutsch, Jean-Luc Perfettini
Radiation therapy is one of the cornerstones of cancer treatment. In tumor cells, exposure to ionizing radiation (IR) provokes DNA damages that trigger various forms of cell death such as apoptosis, necrosis, autophagic cell death, and mitotic catastrophe. IR can also induce cellular senescence that could serve as an additional antitumor barrier in a context-dependent manner. Moreover, accumulating evidence has demonstrated that IR interacts profoundly with tumor-infiltrating immune cells, which cooperatively drive treatment outcomes...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28602975/the-small-molecule-inhibitor-yk-4-279-disrupts-mitotic-progression-of-neuroblastoma-cells-overcomes-drug-resistance-and-synergizes-with-inhibitors-of-mitosis
#12
Madhu Kollareddy, Alice Sherrard, Ji Hyun Park, Marianna Szemes, Kelli Gallacher, Zsombor Melegh, Sebastian Oltean, Martin Michaelis, Jindrich Cinatl, Abderrahmane Kaidi, Karim Malik
Neuroblastoma is a biologically and clinically heterogeneous pediatric malignancy that includes a high-risk subset for which new therapeutic agents are urgently required. As well as MYCN amplification, activating point mutations of ALK and NRAS are associated with high-risk and relapsing neuroblastoma. As both ALK and RAS signal through the MEK/ERK pathway, we sought to evaluate two previously reported inhibitors of ETS-related transcription factors, which are transcriptional mediators of the Ras-MEK/ERK pathway in other cancers...
June 7, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28580168/caml-mediates-survival-of-myc-induced-lymphoma-cells-independent-of-tail-anchored-protein-insertion
#13
Jennifer C Shing, Lonn D Lindquist, Nica Borgese, Richard J Bram
Calcium-modulating cyclophilin ligand (CAML) is an endoplasmic reticulum (ER) protein that functions, along with WRB and TRC40, to mediate tail-anchored (TA) protein insertion into the ER membrane. Physiologic roles for CAML include endocytic trafficking, intracellular calcium signaling, and the survival and proliferation of specialized immune cells, recently attributed to its requirement for TA protein insertion. To identify a possible role for CAML in cancer cells, we generated Eμ-Myc transgenic mice that carry a tamoxifen-inducible deletion allele of Caml...
2017: Cell Death Discovery
https://www.readbyqxmd.com/read/28576750/bzml-a-novel-colchicine-binding-site-inhibitor-overcomes-multidrug-resistance-in-a549-taxol-cells-by-inhibiting-p-gp-function-and-inducing-mitotic-catastrophe
#14
Zhaoshi Bai, Meiqi Gao, Huijuan Zhang, Qi Guan, Jingwen Xu, Yao Li, Huan Qi, Zhengqiang Li, Daiying Zuo, Weige Zhang, Yingliang Wu
Multidrug resistance (MDR) interferes with the efficiency of chemotherapy. Therefore, developing novel anti-cancer agents that can overcome MDR is necessary. Here, we screened a series of colchicine binding site inhibitors (CBSIs) and found that 5-(3, 4, 5-trimethoxybenzoyl)-4-methyl-2-(p-tolyl) imidazol (BZML) displayed potent cytotoxic activity against both A549 and A549/Taxol cells. We further explored the underlying mechanisms and found that BZML caused mitosis phase arrest by inhibiting tubulin polymerization in A549 and A549/Taxol cells...
May 30, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28564580/the-death-pathways-in-mussel-larval-cells-after-a-freeze-thaw-cycle
#15
Nelly A Odintsova, Andrey V Boroda, Mariia A Maiorova, Konstantin V Yakovlev
We analyzed cell viability, caspase activity, plasma membrane alterations and cell ultrastructure morphology to estimate the morphological and biochemical alterations that occur in bivalve molluscan cell cultures during cryopreservation. The use of 5% dymethyl sulfoxide as a cryoprotectant resulted in greater cell survival and a scarcity of destroyed cells lacking cytosol among dead cells. In this case, almost all cells died through necrosis or apoptosis, which appeared to increase in mussel cell cultures after a freeze-thaw cycle...
May 28, 2017: Cryobiology
https://www.readbyqxmd.com/read/28562324/prolonged-mitotic-arrest-induced-by-wee1-inhibition-sensitizes-breast-cancer-cells-to-paclitaxel
#16
Cody W Lewis, Zhigang Jin, Dawn Macdonald, Wenya Wei, Xu Jing Qian, Won Shik Choi, Ruicen He, Xuejun Sun, Gordon Chan
Wee1 kinase is a crucial negative regulator of Cdk1/cyclin B1 activity and is required for normal entry into and exit from mitosis. Wee1 activity can be chemically inhibited by the small molecule MK-1775, which is currently being tested in phase I/II clinical trials in combination with other anti-cancer drugs. MK-1775 promotes cancer cells to bypass the cell-cycle checkpoints and prematurely enter mitosis. In our study, we show premature mitotic cells that arise from MK-1775 treatment exhibited centromere fragmentation, a morphological feature of mitotic catastrophe that is characterized by centromeres and kinetochore proteins that co-cluster away from the condensed chromosomes...
May 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28559472/spermatogonial-deubiquitinase-usp9x-is-essential-for-proper-spermatogenesis-in-mice
#17
Kasane Kishi, Aya Uchida, Hinako M Takase, Hitomi Suzuki, Masamichi Kurohmaru, Naoki Tsunekawa, Masami Kanai-Azuma, Stephen A Wood, Yoshiakira Kanai
USP9X (ubiquitin-specific peptidase 9, X chromosome) is the mammalian orthologue of Drosophila deubiquitinase fat facets that was previously shown to regulate the maintenance of the germ cell lineage partially through stabilizing Vasa, one of the widely conserved factors crucial for gametogenesis. Here, we demonstrate that USP9X is expressed in the gonocytes and spermatogonia in mouse testes from newborn to adult stages. By using Vasa-Cre mice, germ cell-specific conditional deletion of Usp9x from the embryonic stage showed no abnormality in the developing testes by 1 week and no appreciable defects in the undifferentiated and differentiating spermatogonia at postnatal and adult stages...
August 2017: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/28550769/mk-8776-a-novel-chk1-inhibitor-exhibits-an-improved-radiosensitizing-effect-compared-to-ucn-01-by-exacerbating-radiation-induced-aberrant-mitosis
#18
Motofumi Suzuki, Tohru Yamamori, Tomoki Bo, Yuri Sakai, Osamu Inanami
Checkpoint kinase 1 (Chk1) is an evolutionarily conserved serine/threonine kinase that plays an important role in G2/M checkpoint signaling. Here, we evaluate the radiosensitizing effects of a novel selective Chk1 inhibitor MK-8776, comparing its efficacy with a first-generation Chk1 inhibitor UCN-01, and attempt to elucidate the mechanism of radiosensitization. In a clonogenic survival assay, MK-8776 demonstrated a more pronounced radiosensitizing effect than UCN-01, with lower cytotoxicity. Importantly, radiosensitization by MK-8776 can be achieved at doses as low as 2...
May 24, 2017: Translational Oncology
https://www.readbyqxmd.com/read/28542137/dt-13-synergistically-enhanced-vinorelbine-mediated-mitotic-arrest-through-inhibition-of-foxm1-bicd2-axis-in-non-small-cell-lung-cancer-cells
#19
Hongyang Li, Li Sun, Hang Li, Xiaodan Lv, Herve Semukunzi, Ruiming Li, Jun Yu, Shengtao Yuan, Sensen Lin
Non-small-cell lung cancer (NSCLC) is the most commonly diagnosed malignant disease with the leading cause of cancer-related death. Combination treatment remains the major strategy in the clinical therapy of NSCLC. Vinorelbine (NVB), a semi-synthetic vinca alkaloid, is used for advanced and metastatic NSCLC by destabilizing microtubule formation to induce mitotic arrest and cell death. However, the side effect of NVB heavily affected its effectiveness in clinical therapy. Hence, it is of great significance to develop new agents to synergize with NVB and decrease the adverse effect...
May 25, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28536438/optimizing-radiotherapy-protocols-using-computer-automata-to-model-tumour-cell-death-as-a-function-of-oxygen-diffusion-processes
#20
Perrine Paul-Gilloteaux, Vincent Potiron, Grégory Delpon, Stéphane Supiot, Sophie Chiavassa, François Paris, Sylvain V Costes
The concept of hypofractionation is gaining momentum in radiation oncology centres, enabled by recent advances in radiotherapy apparatus. The gain of efficacy of this innovative treatment must be defined. We present a computer model based on translational murine data for in silico testing and optimization of various radiotherapy protocols with respect to tumour resistance and the microenvironment heterogeneity. This model combines automata approaches with image processing algorithms to simulate the cellular response of tumours exposed to ionizing radiation, modelling the alteration of oxygen permeabilization in blood vessels against repeated doses, and introducing mitotic catastrophe (as opposed to arbitrary delayed cell-death) as a means of modelling radiation-induced cell death...
May 23, 2017: Scientific Reports
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