scholarly journals Nuclear Localization Is Not Required for Tip60 Tumor Suppressor Activity in Breast and Lung Cancer Cells

2020 ◽  
Vol 39 (11) ◽  
pp. 2077-2084
Author(s):  
Priyadarshini Ravichandran ◽  
Simon A. Davis ◽  
Himali Vashishtha ◽  
Azad L. Gucwa ◽  
Daniel S. Ginsburg
Keyword(s):  
Lung Cancer ◽  
Tumor Suppressor ◽  
Cancer Cells ◽  
Nuclear Localization ◽  
Lung Cancer Cells ◽  
Suppressor Activity ◽  
Tumor Suppressor Activity

Effect of the actin- and calcium-regulating activities of ITPKB on the metastatic potential of lung cancer cells

2018 ◽  
Vol 475 (12) ◽  
pp. 2057-2071 ◽  
Author(s):  
Selina Bäder ◽  
Elina Glaubke ◽  
Saskia Grüb ◽  
Stefanie Muhs ◽  
Jasmin Wellbrock ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Tumor Suppressor ◽  
Cancer Cells ◽  
Calcium Release ◽  
Lung Cancer Cells ◽  
Actin Dynamics ◽  
Human Lung Cancer ◽  
Suppressor Activity ◽  
Tumor Suppressor Activity ◽  
Actin Structure

Inositol-1,4,5-trisphosphate 3-kinase-A (ITPKA) exhibits oncogenic activity in lung cancer cells by regulating Ins(1,4,5)P3-mediated calcium release and cytoskeletal dynamics. Since, in normal cells, ITPKA is mainly expressed in the brain, it is an excellent target for selected therapy of lung cancer. However, ITPKB is strongly expressed in normal lung tissues, but is down-regulated in lung cancer cells by miR-375, assuming that ITPKB might have tumor suppressor activity. In addition, ITPKB binds to F-actin making it likely that, similar to ITPKA, it controls actin dynamics. Thus, the treatment of ITPKA-expressing lung cancer with ITPKA inhibitors simultaneously inhibiting ITPKB may counteract the therapy. Based on these considerations, we analyzed if ITPKB controls actin dynamics and if the protein reduces aggressive progression of lung cancer cells. We found that ITPKB bundled F-actin in cell-free systems. However, the stable expression of ITPKB in H1299 lung cancer cells, exhibiting very low endogenous ITPKB expression, had no significant effect on the actin structure. In addition, our data show that ITPKB negatively controls transmigration of H1299 cells in vitro by blocking Ins(1,4,5)P3-mediated calcium release. On the other hand, colony formation was stimulated by ITPKB, independent of Ins(1,4,5)P3-mediated calcium signals. However, dissemination of H1299 cells from the skin to the lung in NOD scid gamma mice was not significantly affected by ITPKB expression. In summary, ITPKB does not affect the cellular actin structure and does not suppress dissemination of human lung cancer cells in mice. Thus, our initial hypotheses that ITPKB exhibits tumor suppressor activity could not be supported.

TAp73α Increases p53 Tumor Suppressor Activity in Thyroid Cancer Cells via the Inhibition of Mdm2-Mediated Degradation

2008 ◽  
Vol 6 (1) ◽  
pp. 64-77 ◽  
Author(s):  
Roberta Malaguarnera ◽  
Veronica Vella ◽  
Giuseppe Pandini ◽  
Mariangela Sanfilippo ◽  
Vincenzo Pezzino ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Tumor Suppressor ◽  
Cancer Cells ◽  
Suppressor Activity ◽  
P53 Tumor Suppressor ◽  
Tumor Suppressor Activity ◽  
Thyroid Cancer Cells

scholarly journals Mortaparib, a novel dual inhibitor of mortalin and PARP1, is a potential drug candidate for ovarian and cervical cancers

2019 ◽  
Vol 38 (1) ◽  
Author(s):  
Jayarani F. Putri ◽  
Priyanshu Bhargava ◽  
Jaspreet Kaur Dhanjal ◽  
Tomoko Yaguchi ◽  
Durai Sundar ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Growth Arrest ◽  
Suppressor Activity ◽  
Dual Inhibitor ◽  
Tumor Suppressor Activity ◽  
And Migration

Abstract Background Mortalin is enriched in a large variety of cancers and has been shown to contribute to proliferation and migration of cancer cells in multiple ways. It has been shown to bind to p53 protein in cell cytoplasm and nucleus causing inactivation of its tumor suppressor activity in cancer cells. Several other activities of mortalin including mitochondrial biogenesis, ATP production, chaperoning, anti-apoptosis contribute to pro-proliferative and migration characteristics of cancer cells. Mortalin-compromised cancer cells have been shown to undergo apoptosis in in vitro and in vivo implying that it could be a potential target for cancer therapy. Methods We implemented a screening of a chemical library for compounds with potential to abrogate cancer cell specific mortalin-p53 interactions, and identified a new compound (named it as Mortaparib) that caused nuclear enrichment of p53 and shift in mortalin from perinuclear (typical of cancer cells) to pancytoplasmic (typical of normal cells). Biochemical and molecular assays were used to demonstrate the effect of Mortaparib on mortalin, p53 and PARP1 activities. Results Molecular homology search revealed that Mortaparib is a novel compound that showed strong cytotoxicity to ovarian, cervical and breast cancer cells. Bioinformatics analysis revealed that although Mortaparib could interact with mortalin, its binding with p53 interaction site was not stable. Instead, it caused transcriptional repression of mortalin leading to activation of p53 and growth arrest/apoptosis of cancer cells. By extensive computational and experimental analyses, we demonstrate that Mortaparib is a dual inhibitor of mortalin and PARP1. It targets mortalin, PARP1 and mortalin-PARP1 interactions leading to inactivation of PARP1 that triggers growth arrest/apoptosis signaling. Consistent with the role of mortalin and PARP1 in cancer cell migration, metastasis and angiogenesis, Mortaparib-treated cells showed inhibition of these phenotypes. In vivo tumor suppression assays showed that Mortaparib is a potent tumor suppressor small molecule and awaits clinical trials. Conclusion These findings report (i) the discovery of Mortaparib as a first dual inhibitor of mortalin and PARP1 (both frequently enriched in cancers), (ii) its molecular mechanism of action, and (iii) in vitro and in vivo tumor suppressor activity that emphasize its potential as an anticancer drug.

The 3p21.3 tumor suppressor RBM5 resensitizes cisplatin-resistant human non-small cell lung cancer cells to cisplatin

2012 ◽  
Vol 36 (5) ◽  
pp. 481-489 ◽  
Author(s):  
Ping Li ◽  
Ke Wang ◽  
Jie Zhang ◽  
Lijing Zhao ◽  
Hong Liang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Tumor Suppressor ◽  
Small Cell Lung Cancer ◽  
Cancer Cells ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Lung Cancer Cells ◽  
Small Cell Lung

scholarly journals Bmi1 regulates cell fate via tumor suppressor WWOX repression in small-cell lung cancer cells

2011 ◽  
Vol 102 (5) ◽  
pp. 983-990 ◽  
Author(s):  
Masaki Kimura ◽  
Hisanori Takenobu ◽  
Nobuhiro Akita ◽  
Atsuko Nakazawa ◽  
Hidemasa Ochiai ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Tumor Suppressor ◽  
Small Cell Lung Cancer ◽  
Cancer Cells ◽  
Cell Fate ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Lung Cancer Cells ◽  
Small Cell Lung

scholarly journals Drosophila caliban, a nuclear export mediator, can function as a tumor suppressor in human lung cancer cells

Oncogene ◽  
2005 ◽  
Vol 24 (56) ◽  
pp. 8229-8239 ◽  
Author(s):  
Xiaolin Bi ◽  
Tamara Jones ◽  
Fatima Abbasi ◽  
Heuijung Lee ◽  
Brian Stultz ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Tumor Suppressor ◽  
Cancer Cells ◽  
Nuclear Export ◽  
Human Lung ◽  
Lung Cancer Cells ◽  
Human Lung Cancer ◽  
Human Lung Cancer Cells
Sign in / Sign up

Export Citation Format

Share Document