scholarly journals The role of P63 in cancer, stem cells and cancer stem cells

2011 ◽  
Vol 16 (2) ◽  
Author(s):  
Marta Nekulova ◽  
Jitka Holcakova ◽  
Philip Coates ◽  
Borivoj Vojtesek
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cancer Stem Cells ◽  
Family Members ◽  
Adult Stem Cell ◽  
Epidermal Differentiation ◽  
Protein Isoforms ◽  
P53 Family ◽  
Stem Cell Regulation

AbstractThe transcription factor p63 has important functions in tumorigenesis, epidermal differentiation and stem cell self-renewal. The TP63 gene encodes multiple protein isoforms that have different or even antagonistic roles in these processes. The balance of p63 isoforms, together with the presence or absence of the other p53 family members, p73 and p53, has a striking biological impact. There is increasing evidence that interactions between p53-family members, whether cooperative or antagonistic, are involved in various cell processes. This review summarizes the current understanding of the role of p63 in tumorigenesis, metastasis, cell migration and senescence. In particular, recent data indicate important roles in adult stem cell and cancer stem cell regulation and in the response of cancer cells to therapy.

The role of p63 in epidermal morphogenesis and neoplasia

2010 ◽  
Vol 38 (1) ◽  
pp. 223-228 ◽  
Author(s):  
Simon S. McDade ◽  
Dennis J. McCance
Keyword(s):  
Transcription Factors ◽  
Splice Variants ◽  
Family Members ◽  
Protein Isoforms ◽  
Structural Homology ◽  
P53 Family ◽  
Multiple Protein ◽  
Proliferation And Differentiation ◽  
Epidermal Morphogenesis

The p53 family of transcription factors is made up of p53, p63 and p73, which share significant structural homology. In particular, transcriptional complexity and the expression of multiple protein isoforms are an emergent trait of all family members. p63 is the evolutionarily eldest member of the p53 family and the various isoforms have critical roles in the development of stratifying epithelia. Recent results have uncovered additional splice variants, adding to the complexity of the transcriptional architecture of p63. These observations and the emerging extensive interplay between p63 and p53 in development, proliferation and differentiation underline the importance of considering all isoforms and family members in studies of the function of p53 family members.

scholarly journals LncRNA ASAP1-IT1 enhances cancer cell stemness via regulating miR-509-3p/YAP1 axis in NSCLC

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yantao Liu ◽  
Yuping Yang ◽  
Lingli Zhang ◽  
Jiaqiang Lin ◽  
Bin Li ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Growth ◽  
Cancer Stem Cells ◽  
Tumor Growth ◽  
Cancer Cell ◽  
Qrt Pcr

Abstract Background Non-small cell lung cancer (NSCLC) is a major cause of cancer-related death worldwide, and cancer stem cell is responsible for the poor clinical outcome of NSCLC. Previous reports indicated that long noncoding RNAs (lncRNAs) play important roles in maintaining cancer stemness, however, the underlying mechanisms remain unclear. This study investigates the role of ASAP1 Intronic Transcript 1 (ASAP1-IT1) in cancer cell stemness of NSCLC. Methods The expression of ASAP1-IT1, microRNA-509-3p (miR-509-3p) and apoptosis-/stemness-related genes was analyzed by qRT-PCR in NSCLC tissues, cancer cells and spheres of cancer stem cells. Knockdown of ASAP1-IT1 or overexpression of miR-509-3p in NSCLC cells by infection or transfection of respective plasmids. Sphere formation and colony formation were used to detect NSCLC stem cell-like properties and tumor growth in vitro. Luciferase reporter assays, RNA immunoprecitation (RIP) and qRT-PCR assays were used to analyze the interaction between lncRNA and miRNA. The expression of expression of regulated genes of ASAP1-IT1/miR-509-3p axis was evaluated by qRT-PCR and Western blot. The NSCLC xenograft mouse model was used to validate the role of ASAP1-IT1 in NSCLC stemness and tumor growth in vivo. Results ASAP1-IT1 was up-regulated in NSCLC tissues, cancer cells, and in spheres of A549-derived cancer stem cells. Downregulation of ASAP1-IT1 or overexpression of miR-509-3p significantly decreased cell colony formation and stem cell-like properties of A549-dereived stem cells with decreased expression of stem cell biomarkers SOX2, CD34, and CD133, and suppressing the expression of cell growth-related genes, Cyclin A1, Cyclin B1, and PCNA. Furthermore, knockdown of ASAP1-IT1 or overexpression of miR-509-3p repressed tumor growth in nude mice via reducing expression of tumorigenic genes. ASAP1-IT1 was found to interact with miR-509-3p. Moreover, overexpression of ASAP1-IT1 blocked the inhibition by miR-509-3p on stem cell-like properties and cell growth of A549-dereived stem cells both in vitro and in vivo. Finally, the level of YAP1 was regulated by ASAP1-IT1 and miR-509-3p. Conclusions YAP1-involved ASAP1-IT1/miR-509-3p axis promoted NSCLC progression by regulating cancer cell stemness, and targeting this signaling pathway could be is a promising therapeutic strategy to overcome NSCLC stemness.

scholarly journals miRNA function and modulation in stem cells and cancer stem cells

2014 ◽  
Vol 1 (1) ◽  
Author(s):  
Andrew J. DeCastro ◽  
James DiRenzo
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cancer Stem Cells ◽  
Cell Phenotype ◽  
Pluripotent State ◽  
Differentiated Cells ◽  
Non Coding Rnas ◽  
Multicellular Organisms ◽  
Stem Cell Phenotype

AbstractStem cells belong to a unique class of cells that is collectively responsible for the development and subsequent maintenance of all tissues comprising multicellular organisms. These cells possess unique characteristics that allow them to remain in a pluripotent state, while also continuing to generate differentiated cells. microRNAs, a specialized class of non-coding RNAs, are integral components of the network of pathways that modulates this combination of abilities. This review highlights recent discoveries about the roles miRNAs play in governing stem cell phenotype, and discusses the potential therapeutic utility that miRNAs may have in the treatment of multiple diseases. Additionally, it addresses a novel mode of regulation of stem cell phenotype through lincRNA-mediated modulation of select miRNAs, and the role of secreted, stem cell-derived miRNAs in exerting a paracrine influence on surrounding non-stem cells.

scholarly journals Loss of PRC1 activity in different stem cell compartments activates a common transcriptional program with cell type–dependent outcomes

2019 ◽  
Vol 5 (5) ◽  
pp. eaav1594 ◽  
Author(s):  
Silvia Pivetti ◽  
Daniel Fernandez-Perez ◽  
Alessandro D’Ambrosio ◽  
Caterina Maria Barbieri ◽  
Daria Manganaro ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Transcription Factors ◽  
Transcriptional Repression ◽  
Adult Stem Cell ◽  
Cell Identity ◽  
General Role ◽  
Hair Follicle Stem Cells ◽  
Ectopic Activation

Polycomb repressive complexes are evolutionarily conserved complexes that maintain transcriptional repression during development and differentiation to establish and preserve cell identity. We recently described the fundamental role of PRC1 in preserving intestinal stem cell identity through the inhibition of non–lineage-specific transcription factors. To further elucidate the role of PRC1 in adult stem cell maintenance, we now investigated its role in LGR5+ hair follicle stem cells during regeneration. We show that PRC1 depletion severely affects hair regeneration and, different from intestinal stem cells, derepression of its targets induces the ectopic activation of an epidermal-specific program. Our data support a general role of PRC1 in preserving stem cell identity that is shared between different compartments. However, the final outcome of the ectopic activation of non–lineage-specific transcription factors observed upon loss of PRC1 is largely context-dependent and likely related to the transcription factors repertoire and specific epigenetic landscape of different cellular compartments.

T1150 Role of Cyclooxygenase-2 in Cancer Stem Cell Biology and Effect of COX-2 Inhibitors in Anti-Cancer Therapy Targeting Cancer Stem Cells

2010 ◽  
Vol 138 (5) ◽  
pp. S-499
Author(s):  
Masahiko Tsujii ◽  
Jumpei Kondo ◽  
Tomofumi Akasaka ◽  
Ying Jin ◽  
Yoshito Hayashi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cancer Stem Cells ◽  
Cancer Stem Cell ◽  
Cell Biology ◽  
Stem Cell Biology ◽  
Anti Cancer ◽  
Cox 2 ◽  
Cox 2 Inhibitors

scholarly journals p53 family members regulate cancer stem cells

Cell Cycle ◽  
2016 ◽  
Vol 15 (11) ◽  
pp. 1403-1404 ◽  
Author(s):  
Subhasree Basu ◽  
Maureen E. Murphy
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Family Members ◽  
P53 Family

scholarly journals The Role of Breast Cancer Stem Cells in Chemoresistance and Metastasis in Triple-Negative Breast Cancer

Cancers ◽  
2021 ◽  
Vol 13 (24) ◽  
pp. 6209
Author(s):  
Lin He ◽  
Neda Wick ◽  
Sharon Koorse Germans ◽  
Yan Peng
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Stem Cell ◽  
Cancer Stem Cells ◽  
Cancer Stem Cell ◽  
Triple Negative Breast Cancer ◽  
Targeted Therapies ◽  
Triple Negative ◽  
Breast Cancer Stem Cells

Triple negative breast cancer (TNBC) remains an aggressive disease due to the lack of targeted therapies and relatively low rate of response to chemotherapy, which is currently the main treatment modality for TNBC. Breast cancer stem cells (BCSCs) are a small subpopulation of breast tumors and recognized as drivers of tumorigenesis. TNBC tumors are characterized as being enriched for BCSCs. Studies have demonstrated the role of BCSCs as the source of metastatic disease and chemoresistance in TNBC. Multiple targets against BCSCs are now under investigation, with the considerations of either selectively targeting BCSCs or co-targeting BCSCs and non-BCSCs (majority of tumor cells). This review article provides a comprehensive overview of recent advances in the role of BCSCs in TNBC and the identification of cancer stem cell biomarkers, paving the way for the development of new targeted therapies. The review also highlights the resultant discovery of cancer stem cell targets in TNBC and offers summaries of ongoing clinical trials treating chemoresistant breast cancer. We aim to better understand the mutational landscape of BCSCs and explore potential molecular signaling pathways targeting BCSCs to overcome chemoresistance and prevent metastasis in TNBC, ultimately to improve the overall survival of patients with this devastating disease.

scholarly journals The Role of Serotonin in Breast Cancer Stem Cells

Molecules ◽  
2021 ◽  
Vol 26 (11) ◽  
pp. 3171
Author(s):  
William D. Gwynne ◽  
Mirza S. Shakeel ◽  
Adele Girgis-Gabardo ◽  
John A. Hassell
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Stem Cell ◽  
Cancer Stem Cells ◽  
Cancer Stem Cell ◽  
Tumor Cell ◽  
Breast Tumors ◽  
Breast Cancer Stem Cells ◽  
Selective Antagonists

Breast tumors were the first tumors of epithelial origin shown to follow the cancer stem cell model. The model proposes that cancer stem cells are uniquely endowed with tumorigenic capacity and that their aberrant differentiation yields non-tumorigenic progeny, which constitute the bulk of the tumor cell population. Breast cancer stem cells resist therapies and seed metastases; thus, they account for breast cancer recurrence. Hence, targeting these cells is essential to achieve durable breast cancer remissions. We identified compounds including selective antagonists of multiple serotonergic system pathway components required for serotonin biosynthesis, transport, activity via multiple 5-HT receptors (5-HTRs), and catabolism that reduce the viability of breast cancer stem cells of both mouse and human origin using multiple orthologous assays. The molecular targets of the selective antagonists are expressed in breast tumors and breast cancer cell lines, which also produce serotonin, implying that it plays a required functional role in these cells. The selective antagonists act synergistically with chemotherapy to shrink mouse mammary tumors and human breast tumor xenografts primarily by inducing programmed tumor cell death. We hypothesize those serotonergic proteins of diverse activity function by common signaling pathways to maintain cancer stem cell viability. Here, we summarize our recent findings and the relevant literature regarding the role of serotonin in breast cancer.

Brain tumor stem cells and the tumor microenvironment

2008 ◽  
Vol 24 (3-4) ◽  
pp. E27 ◽  
Author(s):  
Rahul Jandial ◽  
Hoisang U ◽  
Michael L. Levy ◽  
Evan Y. Snyder
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Brain Tumor ◽  
Cancer Stem Cells ◽  
Tumor Stem Cells ◽  
Tumor Environment ◽  
Brain Tumor Stem Cells ◽  
Differentiation And Proliferation ◽  
The Brain

✓ Recent advances in stem cell research and developmental neurobiology have uncovered new perspectives from which to investigate various forms of cancer. Specifically, the hypothesis that tumors consist of a subpopulation of malignant cells similar to stem cells is of great interest to scientists and clinicians and has been dubbed the “cancer stem cell hypothesis.” The region in which this assertion is most relevant is within the brain. Cancer stem cells have been isolated from brain tumors that exhibit characteristics of differentiation and proliferation normally seen only in neural stem cells. These cancer stem cells may be responsible for tumor origin, survival, and proliferation. Furthermore, these cells must be considered within their immediate microenvironment when investigating mechanisms of tumorigenesis. Evidence of brain tumor stem cells is reviewed along with the role of tumor environment as the context within which these cells should be understood.

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