APPLICATIONS OF NUCLEAR MICROPROBE ANALYSIS IN CANCER CELL BIOLOGY AND PHARMACOLOGY

1999 ◽  
Vol 09 (03n04) ◽  
pp. 235-244 ◽  
Author(s):  
RICHARD ORTEGA
Keyword(s):  
Cancer Cell ◽  
Anticancer Agents ◽  
Cell Biology ◽  
Microprobe Analysis ◽  
Nuclear Microprobe ◽  
Cellular Pharmacology ◽  
Metal Carcinogenesis ◽  
In Trans ◽  
Particle Backscattering

Nuclear microprobe analysis studies in cancer cell pharmacology and biology carried out at Bordeaux-Gradignan are reported. The cellular pharmacology of two anticancer agents, cis-diammine-dichloroplatinum(II), and 4′-iodo-4′-deoxy-doxorubicin, were investigated, as well as the role of iron in neuroblastoma carcinogenesis, and chromium(III) in trans-generation carcinogenesis. Nuclear microprobe analysis, using PIXE and particle backscattering microanalysis, was able to reveal intracellular and tissue distributions of the elements under investigation. Moreover, the fully quantitative and multi-elemental character of nuclear microprobe analysis offered information on possible mechanisms of drug action, metal carcinogenesis, and interactions with endogenous trace elements in cancer cells.

scholarly journals The Role of the Hedgehog Pathway in Cholangiocarcinoma

Cancers ◽  
2021 ◽  
Vol 13 (19) ◽  
pp. 4774
Author(s):  
Giulia Anichini ◽  
Laura Carrassa ◽  
Barbara Stecca ◽  
Fabio Marra ◽  
Chiara Raggi
Keyword(s):  
Anticancer Agents ◽  
Cell Biology ◽  
Detailed Knowledge ◽  
Molecular Features ◽  
Cell Proliferation And Differentiation ◽  
Predominant Type ◽  
Proliferation And Differentiation ◽  
Cholangiocarcinoma Cell ◽  
Hh Signaling

Cholangiocarcinoma (CCA) is a poorly treatable type of cancer and, along with hepatocellular carcinoma (HCC), is the predominant type of primitive liver cancer in adults. The lack of understanding of CCA biology has slowed down the identification of novel targets and the development of effective treatments. While tumors share some general characteristics, detailed knowledge of specific features is essential for the development of effectively tailored therapeutic approaches. The Hedgehog (HH) signaling cascade regulates stemness biology, embryonal development, tissue homeostasis, and cell proliferation and differentiation. Its aberrant activation has been associated with a variety of solid and hematological human malignancies. Several HH-inhibiting compounds have been indeed developed as potential anticancer agents in different types of tumors, with Smoothened and GLI inhibitors showing the most promising results. Beside its well-established function in other tumors, findings regarding the HH signaling in CCA are still controversial. Here we will give an overview of the most important clinical and molecular features of cholangiocarcinoma, and we will discuss the available evidence of the crosstalk between the HH signaling pathway and the cholangiocarcinoma cell biology.

scholarly journals The autophagy protein Ambra1 regulates gene expression by supporting novel transcriptional complexes

2020 ◽  
Vol 295 (34) ◽  
pp. 12045-12057
Author(s):  
Christina Schoenherr ◽  
Adam Byron ◽  
Billie Griffith ◽  
Alexander Loftus ◽  
Jimi C. Wills ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cancer Cell ◽  
Cell Invasion ◽  
Cell Biology ◽  
Protein Complexes ◽  
Transcriptional Regulators ◽  
Adaptor Proteins ◽  
Nuclear Pore ◽  
Biochemical Fractionation

Ambra1 is considered an autophagy and trafficking protein with roles in neurogenesis and cancer cell invasion. Here, we report that Ambra1 also localizes to the nucleus of cancer cells, where it has a novel nuclear scaffolding function that controls gene expression. Using biochemical fractionation and proteomics, we found that Ambra1 binds to multiple classes of proteins in the nucleus, including nuclear pore proteins, adaptor proteins such as FAK and Akap8, chromatin-modifying proteins, and transcriptional regulators like Brg1 and Atf2. We identified biologically important genes, such as Angpt1, Tgfb2, Tgfb3, Itga8, and Itgb7, whose transcription is regulated by Ambra1-scaffolded complexes, likely by altering histone modifications and Atf2 activity. Therefore, in addition to its recognized roles in autophagy and trafficking, Ambra1 scaffolds protein complexes at chromatin, regulating transcriptional signaling in the nucleus. This novel function for Ambra1, and the specific genes impacted, may help to explain the wider role of Ambra1 in cancer cell biology.

scholarly journals PRMT5 promotes cancer cell migration and invasion through the E2F pathway

2020 ◽  
Vol 11 (7) ◽  
Author(s):  
Wojciech Barczak ◽  
Li Jin ◽  
Simon Mark Carr ◽  
Shonagh Munro ◽  
Samuel Ward ◽  
...  
Keyword(s):  
Cell Migration ◽  
Cancer Cell ◽  
Cell Biology ◽  
Arginine Methylation ◽  
Migration And Invasion ◽  
Genome Wide ◽  
A Genome ◽  
Important Pathway ◽  
Major Target

Abstract The pRb-E2F pathway is a critical point of regulation in the cell cycle and loss of control of the pathway is a hallmark of cancer. E2F1 is the major target through which pRb exerts its effects and arginine methylation by PRMT5 plays a key role in dictating E2F1 activity. Here we have explored the functional role of the PRMT5-E2F1 axis and highlight its influence on different aspects of cancer cell biology including viability, migration, invasion and adherence. Through a genome-wide expression analysis, we identified a distinct set of genes under the control of PRMT5 and E2F1, including some highly regulated genes, which influence cell migration, invasio and adherence through a PRMT5-dependent mechanism. Most significantly, a coincidence was apparent between the expression of PRMT5 and E2F1 in human tumours, and elevated levels of PRMT5 and E2F1 correlated with poor prognosis disease. Our results suggest a causal relationship between PRMT5 and E2F1 in driving the malignant phenotype and thereby highlight an important pathway for therapeutic intervention.

The role of Sp1 and Sp3 in normal and cancer cell biology

2010 ◽  
Vol 192 (5) ◽  
pp. 275-283 ◽  
Author(s):  
Lin Li ◽  
James R. Davie
Keyword(s):  
Cancer Cell ◽  
Cell Biology

scholarly journals hBfl-1/hNOXA Interaction Studies Provide New Insights on the Role of Bfl-1 in Cancer Cell Resistance and for the Design of Novel Anticancer Agents

2016 ◽  
Vol 12 (2) ◽  
pp. 444-455 ◽  
Author(s):  
Elisa Barile ◽  
Guya D. Marconi ◽  
Surya K. De ◽  
Carlo Baggio ◽  
Luca Gambini ◽  
...  
Keyword(s):  
Cancer Cell ◽  
Anticancer Agents ◽  
Cell Resistance ◽  
Interaction Studies

scholarly journals A neomorphic cancer cell-specific role of MAGE-A4 in trans-lesion synthesis

2016 ◽  
Vol 7 (1) ◽  
Author(s):  
Yanzhe Gao ◽  
Elizabeth Mutter-Rottmayer ◽  
Alicia M. Greenwalt ◽  
Dennis Goldfarb ◽  
Feng Yan ◽  
...  
Keyword(s):  
Cancer Cell ◽  
Specific Role ◽  
In Trans

scholarly journals KH-type splicing regulatory protein controls colorectal cancer cell growth and modulates the tumor microenvironment

2018 ◽  
Author(s):  
Francesco Caiazza ◽  
Katarzyna Oficjalska ◽  
Miriam Tosetto ◽  
James J. Phelan ◽  
Sinéad Noonan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Fate ◽  
Cancer Cell ◽  
In Silico ◽  
Cell Biology ◽  
Ex Vivo ◽  
Regulatory Protein ◽  
Nucleic Acid Binding ◽  
Metastatic Setting

ABSTRACTKH-type splicing regulatory protein (KHSRP) is a multifunctional nucleic acid binding protein implicated in key aspects of cancer cell biology: inflammation and cell-fate determination. However, the role KHSRP plays in colorectal cancer (CRC) tumorigenesis remains largely unknown. Using a combination ofin silicoanalysis of large datasets,ex vivoanalysis of protein expression in patients, and mechanistic studies usingin vitromodels of CRC, we investigated the oncogenic role of KHSRP. We demonstrated KHSRP expression in the epithelial and stromal compartments of both primary and metastatic tumors. Elevated expression was found in tumor versus matched normal tissue, and we validated these findings in larger independent cohortsin silico.KHSRP expression was a prognostic indicator of worse overall survival (HR=3.74, 95% CI = 1.43-22.97, p=0.0138). Mechanistic data in CRC cell line models supported a role of KHSRP in driving epithelial cell proliferation in both a primary and metastatic setting, through control of the G1/S transition. Additionally, KHSRP promoted a pro-angiogenic extracellular environment by regulating the secretion of oncogenic proteins involved in diverse cellular processes such as migration and response to cellular stress. Our study provides novel mechanistic insight into the tumor-promoting effects of KHSRP in CRC.

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