The positive correlation between drug addiction and drug dosage in vemurafenib-resistant melanoma cells is underpinned by activation of ERK1/2-FRA-1 pathway

Rao, Minla; Shi, Benyan; Yuan, Yuan; Wang, Ying; Chen, Yilin; Liu, Xiaoyu; Li, Xiaohua; Zhang, Mingmeng; Liu, Xinguang; Sun, Xiaoyan

doi:10.1097/cad.0000000000000951

Cited by 5 publications

(2 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In several MAPKi-resistant melanoma cell lines harboring different BRAF or NRAS mutations, the ERK hyperphosphorylation induced by drug withdrawal stimulates the p38-Fra-1-CDKN1A signaling axis, which results in p21 accumulation and proliferative arrest [82]. Moreover, conditioned media from drug-depleted vemurafenib-resistant cells inhibit the growth of untreated cells, thus suggesting the role of some growth-inhibitory secreted factor(s) regulated by Fra-1/JunB [83].…”

Section: Fra-1 In Drug Resistance and Drug Addiction Mechanismsmentioning

confidence: 99%

The Fra-1/AP-1 Oncoprotein: From the “Undruggable” Transcription Factor to Therapeutic Targeting

Casalino

Talotta²,

Cimmino

et al. 2022

Cancers

View full text Add to dashboard Cite

The genetic and epigenetic changes affecting transcription factors, coactivators, and chromatin modifiers are key determinants of the hallmarks of cancer. The acquired dependence on oncogenic transcriptional regulators, representing a major determinant of cancer cell vulnerability, points to transcription factors as ideal therapeutic targets. However, given the unavailability of catalytic activities or binding pockets for small-molecule inhibitors, transcription factors are generally regarded as undruggable proteins. Among components of the AP-1 complex, the FOS-family transcription factor Fra-1, encoded by FOSL1, has emerged as a prominent therapeutic target. Fra-1 is overexpressed in most solid tumors, in response to the BRAF-MAPK, Wnt-beta-catenin, Hippo-YAP, IL-6-Stat3, and other major oncogenic pathways. In vitro functional analyses, validated in onco-mouse models and corroborated by prognostic correlations, show that Fra-1-containing dimers control tumor growth and disease progression. Fra-1 participates in key mechanisms of cancer cell invasion, Epithelial-to-Mesenchymal Transition, and metastatic spreading, by driving the expression of EMT-inducing transcription factors, cytokines, and microRNAs. Here we survey various strategies aimed at inhibiting tumor growth, metastatic dissemination, and drug resistance by interfering with Fra-1 expression, stability, and transcriptional activity. We summarize several tools aimed at the design and tumor-specific delivery of Fra-1/AP-1-specific drugs. Along with RNA-based therapeutics targeting the FOSL1 gene, its mRNA, or cognate regulatory circRNAs, we will examine the exploitation of blocking peptides, small molecule inhibitors, and innovative Fra-1 protein degraders. We also consider the possible caveats concerning Fra-1 inhibition in specific therapeutic contexts. Finally, we discuss a recent suicide gene therapy-based approach, aimed at selectively killing the Fra-1-overexpressing neoplastic cells.

show abstract

Section: Fra-1 In Drug Resistance and Drug Addiction Mechanismsmentioning

confidence: 99%

The Fra-1/AP-1 Oncoprotein: From the “Undruggable” Transcription Factor to Therapeutic Targeting

Casalino

Talotta²,

Cimmino

et al. 2022

Cancers

View full text Add to dashboard Cite

show abstract

“…All of them were maintained in Dulbecco's Modified Eagle Medium (DMEM) containing 10% FBS (Gibco, Carlsbad, CA, USA). The drug‐resistant cell lines (A375 R0.5, A375 R2.0) were established by culturing A375 in DMEM supplemented with 10% fetal bovine serum (FBS), 0.5 or 2.0 μM vemurafenib and refreshing 3 or 4 days until more than 90 days [34]. The cells were grown in an incubator at 37°C with 5% CO 2 , when the cells grew to about 70% confluence, they were harvested by trypsin, and finally diluted in 3 mL of phosphate buffer saline (PBS) after 3‐time wash.…”

Section: Methodsmentioning

confidence: 99%

Combining fiber optical tweezers and Raman spectroscopy for rapid identification of melanoma

Qiu

et al. 2022

Journal of Biophotonics

View full text Add to dashboard Cite

Cutaneous melanoma is a skin tumor with a high degree of malignancy and fatality rate, the incidence of which has increased in recent years. Therefore, a rapid and sensitive diagnostic technique of melanoma cells is urgently needed. In this paper, we present a new approach using fiber optical tweezers to manipulate melanoma cells to measure their Raman spectra. Then, combined with Principal Component Analysis and Support Vector Machines (PCA-SVM) classification model, to achieve the classification of common mutant, wild-type and drug-resistant melanoma cells. A total of 150 Raman spectra of 30 cells were collected from mutant, wild-type and drug-resistant melanoma cell lines, and the classification accuracy was 92%, 94%, 97.5%, respectively. These results suggest that the study of tumor cells based on fiber optical tweezers and Raman spectroscopy is a promising method for early and rapid identification and diagnosis of tumor cells.

show abstract

FRA-1: A key factor regulating signal transduction of tumor cells and a potential target molecule for tumor therapy

Zeng

Jin

et al. 2022

Biomedicine & Pharmacotherapy

View full text Add to dashboard Cite

The positive correlation between drug addiction and drug dosage in vemurafenib-resistant melanoma cells is underpinned by activation of ERK1/2-FRA-1 pathway

Cited by 5 publications

References 26 publications

The Fra-1/AP-1 Oncoprotein: From the “Undruggable” Transcription Factor to Therapeutic Targeting

The Fra-1/AP-1 Oncoprotein: From the “Undruggable” Transcription Factor to Therapeutic Targeting

Combining fiber optical tweezers and Raman spectroscopy for rapid identification of melanoma

FRA-1: A key factor regulating signal transduction of tumor cells and a potential target molecule for tumor therapy

Contact Info

Product

Resources

About