Fascin enhances the vulnerability of breast cancer to erastin-induced ferroptosis

Chen, Cong; Xie, Bojian; Li, Zhaoqing; Cao, Feng; Chen, Yongxia; Zhou, Jichun; Ju, Siwei; Zhou, Yulu; Zhang, Xun; Zhuo, Wenying; Yang, Jingjing; Mao, Misha; Xu, Ling; Wang, Linbo

doi:10.1038/s41419-022-04579-1

Cited by 42 publications

(21 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For example, Liu et al identified that OTUB1 (an ovarian tumor family member deubiquitylase) can interact with SLC7A11 to prevent its degradation [35]. Additionally, Chen's study revealed that fascin directly interacts with SLC7A11 and decreases its stability via ubiquitin-mediated degradation [36]. In concert with these findings, we demonstrated that LINC00578 knockdown can promote ubiquitination of SLC7A11.…”

Section: Discussionsupporting

confidence: 73%

Long Noncoding RNA LINC00578 Inhibits Ferroptosis in Pancreatic Cancer via Regulating SLC7A11 Ubiquitination

Wei

Wang

et al. 2023

Oxidative Medicine and Cellular Longevity

View full text Add to dashboard Cite

Background. Pancreatic cancer is a highly aggressive malignancy worldwide with rapid development and an exceedingly poor prognosis. lncRNAs play crucial roles in regulating the biological behaviors of tumor cells. In this study, we discovered that LINC00578 acted as a regulator of ferroptosis in pancreatic cancer. Methods. A series of loss- and gain-of-function experiments in vitro and in vivo were performed to explore the oncogenic role of LINC00578 in pancreatic cancer development and progression. Label-free proteomic analysis was performed to select LINC00578-related differentially expressed proteins. Pull-down and RNA immunoprecipitation assays were carried out to determine and validate the binding protein of LINC00578. Coimmunoprecipitation assays were used to investigate the association of LINC00578 with SLC7A11 in ubiquitination and to confirm the interaction between ubiquitin-conjugating enzyme E2 K (UBE2K) and SLC7A11. An immunohistochemical assay was used to confirm the correlation between LINC00578 and SLC7A11 in the clinic. Results. LINC00578 positively regulated cell proliferation and invasion in vitro and tumorigenesis in vivo in pancreatic cancer. LINC00578 can obviously inhibit ferroptosis events, including cell proliferation, reactive oxygen species (ROS) generation, and mitochondrial membrane potential (MMP) depolarization. In addition, the LINC00578-induced inhibitory effect on ferroptosis events was rescued by SLC7A11 knockdown. Mechanistically, LINC00578 directly binds UBE2K to decrease the ubiquitination of SLC7A11, thus accelerating SLC7A11 expression. In the clinic, LINC00578 is closely associated with clinicopathologic factors and poor prognosis and correlated with SLC7A11 expression in pancreatic cancer. Conclusions. This study elucidated that LINC00578 acts as an oncogene to promote pancreatic cancer cell progression and suppress ferroptosis by directly combining with UBE2K to inhibit the ubiquitination of SLC7A11, which provides a promising option for the diagnosis and treatment of pancreatic cancer.

show abstract

Section: Discussionsupporting

confidence: 73%

Long Noncoding RNA LINC00578 Inhibits Ferroptosis in Pancreatic Cancer via Regulating SLC7A11 Ubiquitination

Wei

Wang

et al. 2023

Oxidative Medicine and Cellular Longevity

View full text Add to dashboard Cite

show abstract

“…Ferroptosis cell death was first discovered in the study of small-molecule inducers for cancer treatment, which provided a new idea for tumor treatment. Many studies have confirmed that ferroptosis in vivo and in vitro is effective against pancreatic cancer, breast cancer, nonsmall cell lung cancer, glioblastoma, and hepatocellular carcinoma cells [89][90][91][92][93][94][95]. More importantly, recent reports show that cancer cells resistant to conventional therapy or tend to metastasize are susceptible to ferroptosis and that the sensitivity of drugresistant cells to chemotherapy and the effect of immunotherapy can be enhanced by ferroptosis [96][97][98][99][100][101][102].…”

Section: Iron-sulfur Clusters and Regulatedmentioning

confidence: 95%

Iron-Sulfur Clusters: A Key Factor of Regulated Cell Death in Cancer

Zhang

Liu

et al. 2022

Oxidative Medicine and Cellular Longevity

View full text Add to dashboard Cite

Iron-sulfur clusters are ancient cofactors that play crucial roles in myriad cellular functions. Recent studies have shown that iron-sulfur clusters are closely related to the mechanisms of multiple cell death modalities. In addition, numerous previous studies have demonstrated that iron-sulfur clusters play an important role in the development and treatment of cancer. This review first summarizes the close association of iron-sulfur clusters with cell death modalities such as ferroptosis, cuprotosis, PANoptosis, and apoptosis and their potential role in cancer activation and drug resistance. This review hopes to generate new cancer therapy ideas and overcome drug resistance by modulating iron-sulfur clusters.

show abstract

“…Then the viability was measured. Working concentrations of Erastin and Ferrostatin-1 were choosen based on previously published data (2-80 μM for Erastin and 0.1-2 μM for Ferrostatin-1) (Dixon et al, 2014;Yu et al, 2019;Anthonymuthu et al, 2021;Li et al, 2021;Chen et al, 2022;Wang et al, 2022).…”

Section: Cell Viability Assaymentioning

confidence: 99%

ELOVL5 and IGFBP6 genes modulate sensitivity of breast cancer cells to ferroptosis

Никулин

Razumovskaya

Poloznikov

et al. 2023

Front. Mol. Biosci.

View full text Add to dashboard Cite

Introduction: Relapse of breast cancer is one of the key obstacles to successful treatment. Previously we have shown that low expression of ELOVL5 and IGFBP6 genes in breast cancer tissue corresponded to poor prognosis. ELOVL5 participates directly in the elongation of polyunsaturated fatty acids (PUFAs) that are considered to play an important role in cancer cell metabolism. Thus, in this work we studied the changes in lipid metabolism in breast cancer cells with reduced expression of either ELOVL5 or IGFBP6 gene.Methods: MDA-MB-231 cells with a stable knockdown of either ELOVL5 or IGFBP6 gene were used in this study. Transcriptomic and proteomic analysis as well as RT-PCR were utilized to assess gene expression. Content of individual fatty acids in the cells was measured with HPLC-MS. HPLC was used for analysis of the kinetics of PUFAs uptake. Cell viability was measured with MTS assay. Flow cytometry was used to measure activation of apoptosis. Fluorescent microscopy was utilized to assess accumulation of ROS and formation of lipid droplets. Glutathione peroxidase activity was measured with a colorimetric assay.Results: We found that the knockdown of IGFBP6 gene led to significant changes in the profile of fatty acids in the cells and in the expression of many genes associated with lipid metabolism. As some PUFAs are known to inhibit proliferation and cause death of cancer cells, we also tested the response of the cells to single PUFAs and to combinations of docosahexaenoic acid (DHA, a n-3 PUFA) with standard chemotherapeutic drugs. Our data suggest that external PUFAs cause cell death by activation of ferroptosis, an iron-dependent mechanism of cell death with excessive lipid peroxidation. Moreover, both knockdowns increased cells’ sensitivity to ferroptosis, probably due to a significant decrease in the activity of the antioxidant enzyme GPX4. Addition of DHA to commonly used chemotherapeutic drugs enhanced their effect significantly, especially for the cells with low expression of IGFBP6 gene.Discussion: The results of this study suggest that addition of PUFAs to the treatment regimen for the patients with low expression of IGFBP6 and ELOVL5 genes can be potentially beneficial and is worth testing in a clinically relevant setting.

show abstract

Fascin enhances the vulnerability of breast cancer to erastin-induced ferroptosis

Cited by 42 publications

References 40 publications

Long Noncoding RNA LINC00578 Inhibits Ferroptosis in Pancreatic Cancer via Regulating SLC7A11 Ubiquitination

Long Noncoding RNA LINC00578 Inhibits Ferroptosis in Pancreatic Cancer via Regulating SLC7A11 Ubiquitination

Iron-Sulfur Clusters: A Key Factor of Regulated Cell Death in Cancer

ELOVL5 and IGFBP6 genes modulate sensitivity of breast cancer cells to ferroptosis

Contact Info

Product

Resources

About