Cell competition-induced apical elimination of transformed cells, EDAC, orchestrates the cellular homeostasis

2021 ◽  
Author(s):  
Shunsuke Kon ◽  
Yasuyuki Fujita
Keyword(s):  
Transformed Cells ◽  
Cell Competition ◽  
Cellular Homeostasis

scholarly journals FBP17-mediated finger-like membrane protrusions in cell competition between normal and RasV12-transformed cells

iScience ◽  
2021 ◽  
pp. 102994
Author(s):  
Tomoko Kamasaki ◽  
Yumi Miyazaki ◽  
Susumu Ishikawa ◽  
Kazuya Hoshiba ◽  
Keisuke Kuromiya ◽  
...  
Keyword(s):  
Transformed Cells ◽  
Cell Competition ◽  
Membrane Protrusions

scholarly journals A role of the sphingosine-1-phosphate (S1P)–S1P receptor 2 pathway in epithelial defense against cancer (EDAC)

2016 ◽  
Vol 27 (3) ◽  
pp. 491-499 ◽  
Author(s):  
Sayaka Yamamoto ◽  
Yuta Yako ◽  
Yoichiro Fujioka ◽  
Mihoko Kajita ◽  
Takeshi Kameyama ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Single Cells ◽  
Initial Step ◽  
Transformed Cells ◽  
Cell Competition ◽  
Positive Role ◽  
Normal Cells ◽  
Apical Extrusion ◽  
Sphingosine 1 Phosphate ◽  
S1p Receptor

At the initial step of carcinogenesis, transformation occurs in single cells within epithelia, where the newly emerging transformed cells are surrounded by normal epithelial cells. A recent study revealed that normal epithelial cells have an ability to sense and actively eliminate the neighboring transformed cells, a process named epithelial defense against cancer (EDAC). However, the molecular mechanism of this tumor-suppressive activity is largely unknown. In this study, we investigated a role for the sphingosine-1-phosphate (S1P)–S1P receptor 2 (S1PR2) pathway in EDAC. First, we show that addition of the S1PR2 inhibitor significantly suppresses apical extrusion of RasV12-transformed cells that are surrounded by normal cells. In addition, knockdown of S1PR2 in normal cells induces the same effect, indicating that S1PR2 in the surrounding normal cells plays a positive role in the apical elimination of the transformed cells. Of importance, not endogenous S1P but exogenous S1P is involved in this process. By using FRET analyses, we demonstrate that S1PR2 mediates Rho activation in normal cells neighboring RasV12-transformed cells, thereby promoting accumulation of filamin, a crucial regulator of EDAC. Collectively these data indicate that S1P is a key extrinsic factor that affects the outcome of cell competition between normal and transformed epithelial cells.

scholarly journals Cell competition with normal epithelial cells promotes apical extrusion of transformed cells through metabolic changes

2017 ◽  
Vol 19 (5) ◽  
pp. 530-541 ◽  
Author(s):  
Shunsuke Kon ◽  
Kojiro Ishibashi ◽  
Hiroto Katoh ◽  
Sho Kitamoto ◽  
Takanobu Shirai ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Metabolic Changes ◽  
Transformed Cells ◽  
Cell Competition ◽  
Apical Extrusion

scholarly journals A cell competition-based drug screen identifies a novel compound that induces dual c-Myc depletion and p53 activation

2020 ◽  
Author(s):  
Dagim Shiferaw Tadele ◽  
Joseph Robertson ◽  
Richard Crispin ◽  
Maria C. Herrera ◽  
Marketa Chlubnova ◽  
...  
Keyword(s):  
Stem Cells ◽  
Transformed Cells ◽  
Drug Screen ◽  
Bone Marrow Niche ◽  
Leukemic Stem Cells ◽  
Cell Competition ◽  
Dna Intercalator ◽  
Strong Activity ◽  
Hematopoietic Stem ◽  
Wide Range

AbstractBCR-Abl is a driver oncogene that causes chronic myeloid leukemia and a subset of acute lymphoid leukemias. Although tyrosine kinase inhibitors provide an effective treatment for these diseases, they generally do not kill leukemic stem cells. Leukemic stem cells are cancer-initiating cells that compete with normal hematopoietic stem cells for the bone marrow niche. Using BCR-Abl as a model oncogene, we performed a drug screen based on competition between isogenic untransformed cells and BCR-Abl-transformed cells, and identified several compounds that selectively target BCR-Abl-transformed cells. Systems-level analysis of one of these novel compounds, DJ34, revealed that it induced depletion of c-Myc and activation of p53. c-Myc depletion occurred in a wide range of tumor types, including leukemia, lymphoma, lung, glioblastoma and breast cancer. Further analyses revealed that DJ34 interferes with c-Myc synthesis at the level of transcription, and we provide data showing that DJ34 is a DNA intercalator and topoisomerase II inhibitor. Physiologically, DJ34 induced apoptosis, cell cycle arrest and cell differentiation, and primary leukemic stem cells were particularly sensitive to DJ34. Taken together, we have identified a novel compound that dually targets c-Myc and p53 in a wide variety of cancers, and with particularly strong activity against leukemic stem cells.

scholarly journals Obesity Suppresses Cell-Competition-Mediated Apical Elimination of RasV12-Transformed Cells from Epithelial Tissues

Cell Reports ◽  
2018 ◽  
Vol 23 (4) ◽  
pp. 974-982 ◽  
Author(s):  
Ayana Sasaki ◽  
Takahiro Nagatake ◽  
Riku Egami ◽  
Guoqiang Gu ◽  
Ichigaku Takigawa ◽  
...  
Keyword(s):  
Transformed Cells ◽  
Cell Competition ◽  
Epithelial Tissues

scholarly journals The cell competition-based high-throughput screening identifies small compounds that promote the elimination of RasV12-transformed cells from epithelia

2015 ◽  
Vol 5 (1) ◽  
Author(s):  
Hajime Yamauchi ◽  
Takanori Matsumaru ◽  
Tomoko Morita ◽  
Susumu Ishikawa ◽  
Katsumi Maenaka ◽  
...  
Keyword(s):  
High Throughput ◽  
High Throughput Screening ◽  
Transformed Cells ◽  
Cell Competition

scholarly journals ZAK Inhibitor PLX4720 Promotes Extrusion of Transformed Cells via Cell Competition

iScience ◽  
2020 ◽  
Vol 23 (7) ◽  
pp. 101327
Author(s):  
Takeshi Maruyama ◽  
Ayana Sasaki ◽  
Sayuri Iijima ◽  
Shiyu Ayukawa ◽  
Nobuhito Goda ◽  
...  
Keyword(s):  
Transformed Cells ◽  
Cell Competition

Mitochondrial hyperfusion: a friend or a foe

2020 ◽  
Vol 48 (2) ◽  
pp. 631-644 ◽  
Author(s):  
Rajdeep Das ◽  
Oishee Chakrabarti
Keyword(s):  
Negative Impact ◽  
Cellular Stress ◽  
Cellular Homeostasis ◽  
Mitochondrial Population

The cellular mitochondrial population undergoes repeated cycles of fission and fusion to maintain its integrity, as well as overall cellular homeostasis. While equilibrium usually exists between the fission–fusion dynamics, their rates are influenced by organellar and cellular metabolic and pathogenic conditions. Under conditions of cellular stress, there is a disruption of this fission and fusion balance and mitochondria undergo either increased fusion, forming a hyperfused meshwork or excessive fission to counteract stress and remove damaged mitochondria via mitophagy. While some previous reports suggest that hyperfusion is initiated to ameliorate cellular stress, recent studies show its negative impact on cellular health in disease conditions. The exact mechanism of mitochondrial hyperfusion and its role in maintaining cellular health and homeostasis, however, remain unclear. In this review, we aim to highlight the different aspects of mitochondrial hyperfusion in either promoting or mitigating stress and also its role in immunity and diseases.

Activin A resistant fetal liver stem/progenitor cells (FLSPC) vigorously repopulate aging rat liver through augmented cell competition

2011 ◽  
Vol 49 (01) ◽  
Author(s):  
A Menthena ◽  
CI Koehler ◽  
JS Sandhu ◽  
MI Yovchev ◽  
E Hurston ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Rat Liver ◽  
Fetal Liver ◽  
Activin A ◽  
Cell Competition ◽  
Aging Rat
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