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https://www.readbyqxmd.com/read/29453319/leptin-signaling-mediates-obesity-associated-csc-enrichment-and-emt-in-preclinical-tnbc-models
#1
Laura W Bowers, Emily L Rossi, Shannon B McDonell, Steven S Doerstling, Subreen A Khatib, Claire G Lineberger, Jody E Albright, Xiaohu Tang, Linda A deGraffenried, Stephen D Hursting
Obesity is associated with poor prognosis in triple-negative breast cancer (TNBC). Preclinical models of TNBC were used to test the hypothesis that increased leptin signaling drives obesity-associated TNBC development by promoting cancer stem cell (CSC) enrichment and/or epithelial-to-mesenchymal transition (EMT). MMTV-Wnt-1 transgenic mice, which develop spontaneous basal-like, triple-negative mammary tumors, received either a control diet (10% kcal from fat) or a diet-induced obesity regimen (DIO, 60% kcal from fat) for up to 42 weeks (n=15/group)...
February 16, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29440169/oncogenic-kinase-induced-pkm2-tyrosine-105-phosphorylation-converts-non-oncogenic-pkm2-to-a-tumor-promoter-and-induces-cancer-stem-like-cells
#2
Zhifen Zhou, Min Li, Lin Zhang, Hong Zhao, Özgür Şahin, Jing Chen, Jean J Zhao, Zhou Songyang, Dihua Yu
The role of pyruvate kinase M2 isoform (PKM2) in tumor progression has been controversial. Previous studies showed that PKM2 promoted tumor growth in xenograft models; however, depletion of PKM2 in the Brca1-loss-driven mammary tumor mouse model accelerates tumor formation. Since oncogenic kinases are frequently activated in tumors and PKM2 phosphorylation promotes tumor growth, we hypothesized that phosphorylation of PKM2 by activated kinases in tumor cells confers PKM2 oncogenic function, whereas non-phosphorylated PKM2 is non-oncogenic...
February 12, 2018: Cancer Research
https://www.readbyqxmd.com/read/29422613/cx26-drives-self-renewal-in-triple-negative-breast-cancer-via-interaction-with-nanog-and-focal-adhesion-kinase
#3
Praveena S Thiagarajan, Maksim Sinyuk, Soumya M Turaga, Erin E Mulkearns-Hubert, James S Hale, Vinay Rao, Abeba Demelash, Caner Saygin, Arnab China, Tyler J Alban, Masahiro Hitomi, Luke A Torre-Healy, Alvaro G Alvarado, Awad Jarrar, Andrew Wiechert, Valery Adorno-Cruz, Paul L Fox, Benjamin C Calhoun, Jun-Lin Guan, Huiping Liu, Ofer Reizes, Justin D Lathia
Tumors adapt their phenotypes during growth and in response to therapies through dynamic changes in cellular processes. Connexin proteins enable such dynamic changes during development, and their dysregulation leads to disease states. The gap junction communication channels formed by connexins have been reported to exhibit tumor-suppressive functions, including in triple-negative breast cancer (TNBC). However, we find that connexin 26 (Cx26) is elevated in self-renewing cancer stem cells (CSCs) and is necessary and sufficient for their maintenance...
February 8, 2018: Nature Communications
https://www.readbyqxmd.com/read/29416846/pml-regulation-and-multifaceted-function-beyond-tumor-suppression
#4
REVIEW
Kuo-Sheng Hsu, Hung-Ying Kao
Promyelocytic leukemia protein (PML) was originally identified as a fusion partner of retinoic acid receptor alpha in acute promyelocytic leukemia patients with the (15;17) chromosomal translocation, giving rise to PML-RARα and RARα-PML fusion proteins. A body of evidence indicated that PML possesses tumor suppressing activity by regulating apoptosis, cell cycle, senescence and DNA damage responses. PML is enriched in discrete nuclear substructures in mammalian cells with 0.2-1 μm diameter in size, referred to as alternately Kremer bodies, nuclear domain 10, PML oncogenic domains or PML nuclear bodies (NBs)...
2018: Cell & Bioscience
https://www.readbyqxmd.com/read/29405062/cerasomal-lovastatin-nanohybrids-for-efficient-inhibition-of-triple-negative-breast-cancer-stem-cells-to-improve-therapeutic-efficacy
#5
Liujiang Song, Xiaojun Tao, Li Lin, Chao Chen, Hui Yao, Guangchun He, Guangyang Zou, Zhong Cao, Shichao Yan, Lu Lu, Huimei Yi, Di Wu, Siyuan Tan, Wanxin Ouyang, Zhifei Dai, Xiyun Deng
Triple-negative breast cancer (TNBC) is a subtype of breast cancer with a higher risk in younger women and a poorer prognosis and without targeted therapies available currently. Cancer stem cells (CSCs) are increasingly recognized as the main cause of treatment failure and tumor recurrence. The present paper reported the encapsulation of lovastatin (LV) into cerasomes incorporating distearoyl phosphatidylcholine (DSPC) and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N -polyethylene glycol 2000 (DSPE-PEG2000) through thin film hydration method in combination with sol-gel reaction and self-assembly process...
February 6, 2018: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29389973/adipocyte-breast-cancer-cell-crosstalk-in-obesity-interferes-with-the-anti-proliferative-efficacy-of-tamoxifen
#6
Lauriane Bougaret, Laetitia Delort, Hermine Billard, Camille Le Huede, Céline Boby, Anne De la Foye, Adrien Rossary, Ali Mojallal, Odile Damour, Céline Auxenfans, Marie Paule Vasson, Florence Caldefie-Chezet
BACKGROUND: Obesity is a well-known risk factor of breast cancer in post-menopausal women that also correlates with a diminished therapeutic response. The influence of adipocytes and their secretome, i.e. adipokines, on the efficacy of hormone therapy has yet to be elucidated. METHODS: We investigated, ex vivo, whether mature adipocytes, differentiated from adipose stem cells of normal-weight (MA20) or obese (MA30) women, and their secretions, were able to counteract the effects of tamoxifen (Tx) which is known to decrease neoplastic cell proliferation...
2018: PloS One
https://www.readbyqxmd.com/read/29389520/the-wnt-signaling-landscape-of-mammary-stem-cells-and-breast-tumors
#7
Caroline M Alexander
Attention has been focused on Wnt signaling in the mouse mammary gland for several decades, firstly by the discovery of several Wnt loci among the oncogenes revealed by MMTV-based insertional mutagenesis screening of mouse mammary gland, and then by the remarkable visualization of Wnt-dependent specification of mammary placodes in embryonic skin. This review aims to summarize the impact of recent data for our understanding of the roles of Wnt signaling in these roles. The amount and identity of both familiar and novel Wnt signaling components is examined for mouse mammary epithelial cells...
January 2018: Progress in Molecular Biology and Translational Science
https://www.readbyqxmd.com/read/29382706/her2-overexpression-triggers-an-il-1%C3%AE-pro-inflammatory-circuit-to-drive-tumorigenesis-and-promote-chemotherapy-resistance
#8
Shou Liu, Ji Shin Lee, Chunfa Jie, Min-Ho Park, Yoichiro Iwakura, Yogin Patel, Mithil Soni, David Reisman, Hexin Chen
Systemic inflammation in breast cancer correlates with poor prognosis but the molecular underpinnings of this connection are not well understood. In this study, we explored the relationship between HER2 overexpression, inflammation and expansion of the mammary stem/progenitor and cancer stem-like cell (CSC) population in breast cancer. HER2-positive epithelial cells initiated and sustained an inflammatory milieu needed to promote tumorigenesis. HER2 induced a feed-forward activation loop of IL-1α and IL-6 that stimulated NF-κB and STAT3 pathways for generation and maintenance of breast CSC...
January 30, 2018: Cancer Research
https://www.readbyqxmd.com/read/29363543/anti-estrogen-therapy-increases-plasticity-and-cancer-stemness-of-prolactin-induced-er%C3%AE-mammary-carcinomas
#9
Michael P Shea, Kathleen A O'Leary, Saja A Fakhraldeen, Vincent Goffin, Andreas Friedl, Kari B Wisinski, Caroline M Alexander, Linda A Schuler
Although anti-estrogen therapies are successful in many patients with estrogen receptor alpha-positive (ERα+) breast cancer, 25-40% fail to respond. Although multiple mechanisms underlie evasion of these treatments, including tumor heterogeneity and drug-resistant cancer stem cells (CSCs), further investigations have been limited by the paucity of preclinical ERα+ tumor models. Here we examined a mouse model of prolactin-induced aggressive ERα+ breast cancer, which mimics the epidemiologic link between prolactin exposure and increased risk for metastatic ERα+ tumors...
January 23, 2018: Cancer Research
https://www.readbyqxmd.com/read/29361573/podoplanin-regulates-mammary-stem-cell-function-and-tumorigenesis-by-potentiating-wnt-%C3%AE-catenin-signaling
#10
Laura Bresson, Marisa M Faraldo, Amandine Di-Cicco, Miguel Quintanilla, Marina A Glukhova, Marie-Ange Deugnier
Stem cells (SC) drive mammary development, giving rise postnatally to an epithelial bilayer composed of luminal and basal myoepithelial cells. Deregulation of SCs is thought to be at the origin of certain breast cancers, however the molecular identity of SCs and the factors regulating their function remain poorly defined. We identified the transmembrane protein, Podoplanin (Pdpn), as a specific marker of the basal compartment, including multipotent SCs, and found Pdpn localized at the basal-luminal interface...
January 22, 2018: Development
https://www.readbyqxmd.com/read/29357008/matricellular-ccn6-wisp3-protein-a-tumor-suppressor-for-mammary-metaplastic-carcinomas
#11
REVIEW
Mai N Tran, Celina G Kleer
Located at 6q22-23, Ccn6 (WISP3) encodes for a matrix-associated protein of the CCN family, characterized by regulatory, rather than structural, roles in development and cancer. CCN6, the least studied member of the CCN family, shares the conserved multimodular structure of CCN proteins, as well as their tissue and cell-type specific functions. In the breast, CCN6 is a critical regulator of epithelial-to-mesenchymal transitions (EMT) and tumor initiating cells. Studies using human breast cancer tissue samples demonstrated that CCN6 messenger RNA and protein are expressed in normal breast epithelia but reduced or lost in aggressive breast cancer phenotypes, especially inflammatory breast cancer and metaplastic carcinomas...
January 22, 2018: Journal of Cell Communication and Signaling
https://www.readbyqxmd.com/read/29344258/involvement-of-breast-cancer-stem-cells-in-tumor-angiogenesis
#12
Yu Wang, Chen Li, Yuqiang Li, Zhitu Zhu
The aim of the present study was to investigate the role of breast cancer stem cells (BCSCs) in the angiogenesis of breast cancer tumors. The expression levels of mutant p53, cluster of differentiation (CD)31, vascular endothelial factor (VEGF), in addition to human epidermal growth factor (HER)2, were detected in the blood vessels of human breast cancer (BC) tissue samples. CD44+/CD24-/low cells were selected from single-cell suspensions of BC tissues to assess the expression of CD31 and CD105, in addition to the ability of these cells to metabolize acetylated low-density lipoprotein (Ac-LDL)...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29341428/epigenetic-silencing-of-tap1-in-aldefluor-breast-cancer-stem-cells-contributes-to-their-enhanced-immune-evasion
#13
Mohammad Sultan, Dejan Vidovic, Arianne S Paine, Thomas T Huynh, Krysta M Coyle, Margaret L Thomas, Brianne M Cruickshank, Cheryl A Dean, Derek R Clements, Youra Kim, Kristin Lee, Shashi A Gujar, Ian C Weaver, Paola Marcato
Avoiding detection and destruction by immune cells is key for tumor initiation and progression. The important role of cancer stem cells (CSC) in tumor initiation has been well established, yet their ability to evade immune detection and targeting is only partly understood. To investigate the ability of breast CSCs to evade immune detection we identified a highly tumorigenic population in a spontaneous murine mammary tumor based on increased aldehyde dehydrogenase (ALDH) activity. We performed tumor growth studies in immunocompetent and immunocompromised mice...
January 17, 2018: Stem Cells
https://www.readbyqxmd.com/read/29339820/histone-variant-macroh2a1-plays-an-isoform-specific-role-in-suppressing-epithelial-mesenchymal-transition
#14
Dayle Q Hodge, Jihong Cui, Matthew J Gamble, Wenjun Guo
Epithelial-Mesenchymal Transition (EMT) is a biological program that plays key roles in various developmental and pathological processes. Although much work has been done on signaling pathways and transcription factors regulating EMT, the epigenetic regulation of EMT remains not well understood. Histone variants have been recognized as a key group of epigenetic regulators. Among them, macroH2A1 is involved in stem cell reprogramming and cancer progression. We postulated that macroH2A1 may play a role in EMT, a process involving reprogramming of cellular states...
January 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29330806/fluorescence-activated-cell-sorting-of-murine-mammary-cancer-stem-like-cell-subpopulations-with-hif-activity
#15
Danielle L Brooks, Tiffany N Seagroves
Fluorescence-activated cell sorting (FACS) is a common method to identify and to isolate subpopulations within a complex mixture of cells based on their light scatter and fluorescent staining profiles. FACS is widely used to enrich for normal tissue and tumor cells that have stem cell potential. Whereas FACS protocols using conventional breast cancer cell lines are relatively routine, additional technical challenges are encountered when sorting for cell populations from freshly digested solid tumors, particularly for use in downstream cancer stem cell (CSC) assays...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29326438/conditional-knockout-of-n-myc-and-stat-interactor-disrupts-normal-mammary-development-and-enhances-metastatic-ability-of-mammary-tumors
#16
Hawley C Pruitt, Brandon J Metge, Shannon E Weeks, Dongquan Chen, Shi Wei, Robert A Kesterson, Lalita A Shevde, Rajeev S Samant
The process of organ development requires a delicate balance between cellular plasticity and differentiation. This balance is disrupted in cancer initiation and progression. N-Myc and STAT interactor (NMI: human or Nmi: murine) has emerged as a relevant player in the etiology of breast cancer. However, a fundamental understanding of its relevance to normal mammary biology is lacking. To gain insight into its normal function in mammary gland, we generated a mammary-specific Nmi knockout mouse model. We observed that Nmi protein expression is induced in mammary epithelium at the onset of pregnancy, in luminal cells and persists throughout lactation...
January 12, 2018: Oncogene
https://www.readbyqxmd.com/read/29320711/anatomical-physiological-and-functional-diversity-of-adipose-tissue
#17
REVIEW
Rachel K Zwick, Christian F Guerrero-Juarez, Valerie Horsley, Maksim V Plikus
Adipose tissue depots can exist in close association with other organs, where they assume diverse, often non-traditional functions. In stem cell-rich skin, bone marrow, and mammary glands, adipocytes signal to and modulate organ regeneration and remodeling. Skin adipocytes and their progenitors signal to hair follicles, promoting epithelial stem cell quiescence and activation, respectively. Hair follicles signal back to adipocyte progenitors, inducing their expansion and regeneration, as in skin scars. In mammary glands and heart, adipocytes supply lipids to neighboring cells for nutritional and metabolic functions, respectively...
January 9, 2018: Cell Metabolism
https://www.readbyqxmd.com/read/29298894/tumor-extrinsic-discoidin-domain-receptor-1-promotes-mammary-tumor-growth-by-regulatingadipose-stromal-interleukin-6-production-in-mice
#18
Xiujie Sun, Kshama Gupta, Bogang Wu, Deyi Zhang, Bin Yuan, Xiaowen Zhang, Huai-Chin Chiang, Chi Zhang, Tyler J Curiel, Michelle P Bendeck, Stephen Hursting, Yanfen Hu, Rong Li
Discoidin domain receptor 1 (DDR1) is a collagen receptor that mediates cell communications with the extracellular matrix (ECM). Aberrant expression and activity of DDR1 in tumor cells are known to promote tumor growth. Although elevated DDR1 levels in stroma of breast tumors are associated with poor patient outcome, a causal role for tumor-extrinsic DDR1 in cancer promotion remains unclear, however. Here, we report that murine mammary tumor cells transplanted to syngeneic recipient mice in which Ddr1 has been knocked out (KO) grow less robustly than in WT mice...
January 3, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29290625/regulation-of-mammary-luminal-cell-fate-and-tumorigenesis-by-p38%C3%AE
#19
Ivan Del Barco Barrantes, Camille Stephan-Otto Attolini, Konstantin Slobodnyuk, Ana Igea, Sara Gregorio, Sylwia Gawrzak, Roger R Gomis, Angel R Nebreda
Mammary stem and progenitor cells are essential for mammary gland homeostasis and are also candidates for cells of origin of mammary tumors. Here, we have investigated the function of the protein kinase p38α in the mammary gland using mice that delete this protein in the luminal epithelial cells. We show that p38α regulates the fate of luminal progenitor cells through modulation of the transcription factor RUNX1, an important controller of the estrogen receptor-positive cell lineage. We also provide evidence that the regulation of RUNX1 by p38α probably involves the kinase MSK1, which phosphorylates histone H3 at the RUNX1 promoter...
December 21, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/29287960/discovering-alkylamide-derivatives-of-bexarotene-as-new-therapeutic-agents-against-triple-negative-breast-cancer
#20
Luxi Chen, Chao Long, Jennifer Nguyen, Dhiraj Kumar, Jiyong Lee
Triple-negative breast cancer (TNBC) has been reported to be correlated with high expression of proliferation markers as well as constitutive activation of metastasis-relevant signaling pathways. For many years, breast cancer researchers have been investigating specific and effective methods to treat or to control the development of TNBC, but promising therapeutic options remain elusive. In this study, we have demonstrated that alkylamide derivatives of bexarotene DK-1-150 and DK-1-166 induce apoptotic cell death in TNBC cell lines without causing cytotoxicity in the normal mammary epithelial cell line...
December 16, 2017: Bioorganic & Medicinal Chemistry Letters
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