Cells, Vol. 9, Pages 90: PP2A Deficiency Enhances Carcinogenesis of Lgr5+ Intestinal Stem Cells Both in Organoids and In Vivo:
Cells, Vol. 9, Pages 90: PP2A Deficiency Enhances Carcinogenesis of Lgr5+ Intestinal Stem Cells Both in Organoids and In Vivo
Cells doi: 10.3390/cells9010090
Authors:
Yu-Ting Yen
May Chien
Yung-Chih Lai
Dao-Peng Chen
Cheng-Ming Chuong
Mien-Chie Hung
Shih-Chieh Hung
In most cancers, cellular origin and the contribution of intrinsic and extrinsic factors toward transformation remain elusive. Cell specific carcinogenesis models are currently unavailable. To investigate cellular origin in carcinogenesis, we developed a tumorigenesis model based on a combination of carcinogenesis and genetically engineered mouse models. We show in organoids that treatment of any of three carcinogens, DMBA, MNU, or PhIP, with protein phosphatase 2A (PP2A) knockout induced tumorigenesis in Lgr5+ intestinal lineage, but not in differentiated cells. These transformed cells increased in stem cell signature, were upregulated in EMT markers, and acquired tumorigenecity. A mechanistic approach demonstrated that tumorigenesis was dependent on Wnt, PI3K, and RAS-MAPK activation. In vivo combination with carcinogen and PP2A depletion also led to tumor formation. Using whole-exome sequencing, we demonstrate that these intestinal tumors display mutation landscape and core driver pathways resembling human intestinal tumor in The Cancer Genome Atlas (TCGA). These data provide a basis for understanding the interplay between extrinsic carcinogen and intrinsic genetic modification and suggest that PP2A functions as a tumor suppressor in intestine carcinogenesis.
How I became a happy woman again
ΑπάντησηΔιαγραφήWith tears of joy and happiness I am giving out my testimony to all viewers on line, my problem with Stomach Cancer stage IB and HIV has caused me many pains and sadness especially in my family.
I was so afraid of loosing my life, I suffered the embarrassment of visiting
therapy hundreds of times, unfortunately they did not find a definitive solution to my problem, I cried all day and night, do I have to live my life this way? I searched all true the internet for care, I was scammed by internet fraudsters times without numbers… until a friend of mine who stays in the UK introduced me to a friend of hers who was cured of the same disease, and she introduced me to Dr Itua who cured her from Breast Cancer by this email/WhatsApp +2348149277967, drituaherbalcenter@gmail.com. I contacted him and he promised that all will be fine and I had faith.He sent me his herbal medicines through Courier service and i was instructed on how to drink it for three weeks to cure,I followed the instruction given to me and Today am a happy woman again. He cures all kind of diseases like,Brain cancer,Gestational trophoblastic disease,Head and neck cancer,Ovarian cancer,Hodgkin lymphoma,Herpes,,Liver cancer,Throat cancer,Syndrome Fibrodysplasia Ossificans ProgresS sclerosis,Alzheimer's disease,Chronic Diarrhea,Copd,Parkinson,Als,Adrenocortical carcinoma Infectious mononucleosis,Intestinal cancer,Thyroid Cancer,Uterine cancer,Fibroid,Angiopathy, Ataxia,Arthritis,Amyotrophic Lateral Sclerosis,Brain Tumor,Fibromyalgia,Fluoroquinolone ToxicityBladder cancer,Hiv,Esophageal cancer,Gallbladder cancer,Kidney cancer,Hpv,Lung cancer,Melanoma,Mesothelioma,Multiple myeloma,Neuroendocrine tumors
Non-Hodgkin lymphoma,Oral cancer,Sinus cancer,Hepatitis A,B/C,Skin cancer,Soft tissue sarcoma,Appendix,Spinal cancer,Stomach cancer,Vaginal cancer,Vulvar cancer,Testicular cancer,Tach Diseases,Leukemia.