Cytoskeletal and Cytoskeleton-Associated Proteins: Key Regulators of Cancer Stem Cell Properties

Li, Yuqiang; Wang, Dan; Ge, Heming; Güngör, Cenap; Gong, Xuejun; Chen, Yongheng

doi:10.3390/ph15111369

Cited by 6 publications

(2 citation statements)

References 306 publications

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“…Because geranylgeranylation of Rho GTPases is fundamental for their downstream effects on cytoskeletal reorganization ( 20 ), which mediates the interaction of cancer stem cells (CSC) with the tumor microenvironment, maintenance of stemness, and CSC migration ( 21 ) we next tested which Rho GTPase would affect the self-renewal capacity of GBM cells ( Fig. 5A ).…”

Section: Resultsmentioning

confidence: 99%

Activation of the Mevalonate Pathway in Response to Anti-cancer Treatments Drives Glioblastoma Recurrences Through Activation of Rac-1

He,

Ioannidis,

Hoffman

et al. 2024

Cancer Research Communications

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Glioblastoma (GBM) is the deadliest adult brain cancer. Under the current standard of care almost all patients succumb to the disease and novel treatments are urgently needed. Recognizing that GBM are addicted to cholesterol, past clinical trials have repurposed statins against GBM but failed. The purpose of this study was to test if treatments that upregulate the cholesterol biosynthesis pathway in GBM would generate a metabolic vulnerability that can be exploited using statins and to determine the underlying mechanisms. Effects of the radiotherapy and temozolomide or dopamine receptor antagonists on the mevalonate pathway in GBM were assessed in in vitro and in vivo. The impact of statins on self-renewal of glioma stem cells and median survival was studied. Branches of the mevalonate pathway were probed to identify relevant effector proteins. Cells surviving combination treatments that converge in activating the immediate early response, universally upregulated the mevalonate pathway and increased stemness of GBM cells through activation of the Rho-GTPase Rac-1. Activation of the mevalonate pathway and Rac-1 was inhibited by statins, which led to improved survival in mouse models of glioblastoma when combined with radiation and drugs that target the glioma stem cell pool and plasticity of glioma cells. We conclude that a combination of dopamine receptor antagonists and statins could potentially improve radiotherapy outcome and warrants further investigation.

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Section: Resultsmentioning

confidence: 99%

Activation of the Mevalonate Pathway in Response to Anti-cancer Treatments Drives Glioblastoma Recurrences Through Activation of Rac-1

He,

Ioannidis,

Hoffman

et al. 2024

Cancer Research Communications

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“…Since previous studies established differential expression levels of chorein in the three rhabdomyosarcoma cell lines ( Honisch et al, 2015b ), our present observations may pointing out a possible correlation between chorein expression levels and interaction to the microtubular network. Conversely, previous studies established that reorganization of cytoskeletal structures including actin microfilaments and modulation of cytoskeletal gene signaling in tumor cells may regulate pivotal cellular functions including cell survival and motility ( Yamazaki, Kurisu & Takenawa, 2005 ; Yilmaz & Christofori, 2009 ; Jaya, 2020 ; Ong et al., 2020 ; Li et al., 2022 ). Accordingly, our study indicates that the microtubule reorganization might contribute to the reported regulation of apoptosis in rhabdomyosarcoma cells upon chorein silencing, as described before ( Honisch et al, 2015b ).…”

Section: Discussionmentioning

confidence: 98%

Chorein sensitive microtubule organization in tumor cells

Alkahtani,

Alkahtane,

Stournaras

et al. 2023

PeerJ

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Background The purpose of this study is to analyzed the involvement of chorein in microtubules organization of three types of malignant; rhabdomyosarcoma tumor cells (ZF), rhabdomyosarcoma cells (RH30), and rhabdomyosarcoma cells (RD). ZF are expressing high chorein levels. Previous studies revealed that chorein protein silencing in ZF tumor cells persuaded apoptotic response followed by cell death. In addition, in numerous malignant and non-malignant cells this protein regulates actin cytoskeleton structure and cellular signaling. However, the function of chorein protein in microtubular organization is yet to be established. Methods In a current research study, we analyzed the involvement of chorein in microtubules organization by using three types of malignant rhabdomyosarcoma cells. We have applied confocal laser-scanning microscopy to analyze microtubules structure and RT-PCR to examine cytoskeletal gene transcription. Results We report here that in rhabdomyosarcoma cells (RH30), chorein silencing induced disarrangement of microtubular network. This was documented by laser scanning microscopy and further quantified by FACS analysis. Interestingly and in agreement with previous reports, tubulin gene transcription in RH cells was unchanged upon silencing of chorein protein. Equally, confocal analysis showed minor disordered microtubules organization with evidently weakened staining in rhabdomyosarcoma cells (RD and ZF) after silencing of chorein protein. Conclusion These results disclose that chorein silencing induces considerable structural disorganization of tubulin network in RH30 human rhabdomyosarcoma tumor cells. Additional studies are now needed to establish the role of chorein in regulating cytoskeleton architecture in tumor cells.

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Synthetic Retinoid Sulfarotene Selectively Inhibits Tumor‐Repopulating Cells of Intrahepatic Cholangiocarcinoma via Disrupting Cytoskeleton by P‐Selectin/PSGL1 N‐Glycosylation Blockage

Du,

Qi,

Chen

et al. 2024

Advanced Science

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Intrahepatic cholangiocarcinoma (ICC) is a highly lethal malignancy that currently lacks effective clinical treatments. Eliminating stem cell‐like cancer cells is an extremely promising but challenging strategy for treating ICC. A recently developed synthetic retinoid, sulfarotene, abrogates proliferation, and induces apoptosis of tumor‐repopulating cells (TRCs) that exhibit stem cell‐like properties, yet its effect and underlying mechanisms remain elusive in ICC. It is found that although 5‐fluorouracil, cisplatin, pemigatinib, and gemcitabine all inhibit ICC‐TRCs, sulfarotene demonstrates superior efficacy. Sulfarotene induces retinoic acid receptor alpha (RARɑ) translocation from the cytoplasm to the nucleus, suppressing P‐selectin expression at the transcriptional level. Moreover, it directly interacts with fucosyltransferase 8 (FUT8), inhibiting the core fucosylation of P‐selectin glycoprotein ligand 1 (PSGL1). These actions collectively inhibit ICC‐TRCs via destroying PSGL1‐regulated cytoskeleton. The findings provide a strategy of inhibiting P‐selectin/PSGL1 interaction and altering PSGL1 glycosylation pattern to compromise the cytoskeletal integrity and eliminate ICC‐TRCs.

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Cytoskeletal and Cytoskeleton-Associated Proteins: Key Regulators of Cancer Stem Cell Properties

Cited by 6 publications

References 306 publications

Activation of the Mevalonate Pathway in Response to Anti-cancer Treatments Drives Glioblastoma Recurrences Through Activation of Rac-1

Activation of the Mevalonate Pathway in Response to Anti-cancer Treatments Drives Glioblastoma Recurrences Through Activation of Rac-1

Chorein sensitive microtubule organization in tumor cells

Synthetic Retinoid Sulfarotene Selectively Inhibits Tumor‐Repopulating Cells of Intrahepatic Cholangiocarcinoma via Disrupting Cytoskeleton by P‐Selectin/PSGL1 N‐Glycosylation Blockage

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