scholarly journals Role of a kinesin motor in cancer cell mechanics

2019 ◽  
Author(s):  
Kalpana Mandal ◽  
Katarzyna Pogoda ◽  
Satabdi Nandi ◽  
Samuel Mathieu ◽  
Amal Kasri ◽  
...  

SummaryMolecular motors play important roles in force generation, migration and intracellular trafficking. Changes in specific motor activities are altered in numerous diseases. KIF20A, a motor protein of the kinesin-6 family, is overexpressed in bladder cancer, and KIF20A levels correlate negatively with the clinical outcome. We report here a new role for the KIF20A kinesin motor protein in intracellular mechanics. Using optical tweezers to probe intracellular mechanics and surface AFM to probe cortical mechanics, we first confirm that bladder cells soften with increasing cancer grade. We then show that inhibiting KIF20A makes the intracellular environment softer for both high and low grade bladder cancer cells. Upon inhibition of KIF20A cortical stiffness also decreases in lower grade cells, while it surprisingly increases in higher grade malignant cells. Changes in cortical stiffness correlate with the interaction of KIF20A with myosin IIA. Moreover, KIF20A negatively regulates bladder cancer cell motility irrespective of the underlying substrate stiffness. Our results reveal a central role for a microtubule motor in cell mechanics and migration in the context of bladder cancer.

Gene ◽  
2020 ◽  
Vol 760 ◽  
pp. 144989
Author(s):  
Anzana Parvin ◽  
Shuang-Li Hao ◽  
Fu-Qing Tan ◽  
Wan-Xi Yang

Molecules ◽  
2021 ◽  
Vol 26 (16) ◽  
pp. 4919
Author(s):  
Canxia He ◽  
Luigina P. Buongiorno ◽  
Wei Wang ◽  
Jonathan C. Y. Tang ◽  
Natalizia Miceli ◽  
...  

Sulforaphane (SFN), an isothiocyanate (ITCs) derived from glucosinolate that is found in cruciferous vegetables, has been reported to exert a promising anticancer effect in a substantial amount of scientific research. However, epidemical studies showed inconsistencies between cruciferous vegetable intake and bladder cancer risk. In this study, human bladder cancer T24 cells were used as in vitro model for revealing the inhibitory effect and its potential mechanism of SFN on cell growth. Here, a low dose of SFN (2.5 µM) was shown to promote cell proliferation (5.18–11.84%) and migration in T24 cells, whilst high doses of SFN (>10 µM) inhibited cell growth significantly. The induction effect of SFN on nuclear factor (erythroid-derived 2)-like 2 (Nrf2) expression at both low (2.5 µM) and high dose (10 µM) was characterized by a bell-shaped curve. Nrf2 and glutathione (GSH) might be the underlying mechanism in the effect of SFN on T24 cell growth since Nrf2 siRNA and GSH-depleting agent L-Buthionine-sulfoximine abolished the effect of SFN on cell proliferation. In summary, the inhibitory effect of SFN on bladder cancer cell growth and migration is highly dependent on Nrf2-mediated GSH depletion and following production. These findings suggested that a higher dose of SFN is required for the prevention and treatment of bladder cancer.


Nano Letters ◽  
2019 ◽  
Vol 19 (11) ◽  
pp. 7691-7702 ◽  
Author(s):  
Kalpana Mandal ◽  
Katarzyna Pogoda ◽  
Satabdi Nandi ◽  
Samuel Mathieu ◽  
Amal Kasri ◽  
...  

2016 ◽  
Vol 7 (14) ◽  
pp. 2132-2138 ◽  
Author(s):  
Liang Dong ◽  
Fan Lin ◽  
Wanjun Wu ◽  
Weiren Huang ◽  
Zhiming Cai

2020 ◽  
Author(s):  
Pallavi Mathur ◽  
Camilla De Barros Santos ◽  
Hugo Lachuer ◽  
Bruno Latgé ◽  
François Radvanyi ◽  
...  

AbstractLate endosomes/lysosomes (endolysosomes) emerge as a potential regulatory hub during cancer. Here, we investigate the intracellular landscape of this organelle in a collection of bladder cancer cell lines and normal human urothelium cells under standardized culture conditions. We find that high-grade bladder cancer cells are characterized by scattered endolysosomes that are accompanied by an altered cellular pH homeostasis and major changes of mTORC1 regulation. Mechanistically, we reveal that mTORC1 substrate specificity is altered, and mTORC1 responsiveness to endolysosome positioning is lost in high-grade cancer cells compared to low-grade cells, highlighting unexpected mechanisms of mTORC1 deregulation in the bladder cancer model. Because endolysosome positioning was critical for invasion from 3D spheroids, our results indicate that changes in their cellular positioning and ability to support signaling, strongly impact cancer cell behavior. Thus, monitoring detailed changes of endolysosomes at different steps of cancer disease reveals intricate spatial and temporal dimensions of tumorigenesis.Statement of significanceOur study reveals significant changes of endolysosomes in bladder cancer progression, highlighting endolysosome dysfunction as a fundamental driving progress in malignancies. The identified alterations in endolysosome positioning and associated mTORC1 signaling regulation could help to stratify emerging therapeutic strategies targeting the endolysosomal compartment.


2020 ◽  
Author(s):  
Tejaswi Iyyanki ◽  
Baozhen Zhang ◽  
Qiushi Jin ◽  
Hongbo Yang ◽  
Tingting Liu ◽  
...  

AbstractMuscle-invasive bladder cancers have recently been characterized by their distinct expression of luminal and basal genes, which could be used to predict key clinical features such as disease progression and overall survival. For example, FOXA1, GATA3, and PPARG have been shown to be essential for luminal subtype-specific regulation and subtype switching, while TP63 and STAT3 are critical for basal subtype bladder cancer. Despite these advances, the underlying epigenetic mechanism and 3D chromatin architecture for subtype-specific regulation in bladder cancers remains largely unknown. Here, we determined the genome-wide transcriptome, enhancer landscape, TF binding profiles (FOXA1 and GATA3) in luminal and basal subtypes of bladder cancers. Furthermore, we mapped genome-wide chromatin interactions by Hi-C in both bladder cancer cell lines and primary patient tumors, for the first time in bladder cancer. We showed that subtype-specific transcription is accompanied by specific open chromatin and epigenomic marks, at least partially driven by distinct TF binding at distal-enhancers of luminal and basal bladder cancers. Finally, we identified a novel clinically relevant transcriptional factor, Neuronal PAS Domain Protein 2 (NPAS2), in luminal bladder cancers that regulates other luminal-specific genes (such as FOXA1, GATA3, and PPARG) and affects cancer cell proliferation and migration. In summary, our work shows a subtype-specific epigenomic and 3D genome structure in urinary bladder cancers and suggested a novel link between the circadian TF NPAS2 and a clinical bladder cancer subtype.


2015 ◽  
Vol 62 (5) ◽  
pp. 628-633 ◽  
Author(s):  
Kai Liang ◽  
Tao Liu ◽  
Ning Chu ◽  
Jian Kang ◽  
Rui Zhang ◽  
...  

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