Invasion and metastasis in cancer: molecular insights and therapeutic targets

Signal Transduction and Targeted Therapy, Journal Year: 2025, Volume and Issue: 10(1)

Published: Feb. 20, 2025

The progression of malignant tumors leads to the development secondary in various organs, including bones, brain, liver, and lungs. This metastatic process severely impacts prognosis patients, significantly affecting their quality life survival rates. Research efforts have consistently focused on intricate mechanisms underlying this corresponding clinical management strategies. Consequently, a comprehensive understanding biological foundations tumor metastasis, identification pivotal signaling pathways, systematic evaluation existing emerging therapeutic strategies are paramount enhancing overall diagnostic treatment capabilities for tumors. However, current research is primarily metastasis within specific cancer types, leaving significant gaps our complex cascade, organ-specific tropism mechanisms, targeted treatments. In study, we examine sequential processes elucidate driving organ-tropic systematically analyze tumors, those tailored organ involvement. Subsequently, synthesize most recent advances technologies challenges opportunities encountered pertaining bone metastasis. Our objective offer insights that can inform future practice crucial field.

Language: Английский

---

DTX2 attenuates Lenvatinib-induced ferroptosis by suppressing docosahexaenoic acid biosynthesis through HSD17B4-dependent peroxisomal β-oxidation in hepatocellular carcinoma

Drug Resistance Updates, Journal Year: 2025, Volume and Issue: 81, P. 101224 - 101224

Published: Feb. 28, 2025

Language: Английский

---

SERPINE2 promotes liver cancer metastasis by inhibiting c‐Cbl‐mediated EGFR ubiquitination and degradation

Cancer Communications, Journal Year: 2024, Volume and Issue: 44(3), P. 384 - 407

Published: Feb. 26, 2024

Liver cancer is a malignancy with high morbidity and mortality rates. Serpin family E member 2 (SERPINE2) has been reported to play key role in the metastasis of many tumors. In this study, we aimed investigate potential mechanism SERPINE2 liver metastasis.

Language: Английский

---

Organoids and spheroids: advanced in vitro models for liver cancer research

Frontiers in Cell and Developmental Biology, Journal Year: 2025, Volume and Issue: 12

Published: Jan. 9, 2025

Liver cancer is a leading cause of cancer-related deaths worldwide, highlighting the need for innovative approaches to understand its complex biology and develop effective treatments. While traditional in vivo animal models have played vital role liver research, ethical concerns demand more human-relevant systems driven development advanced vitro models. Spheroids organoids emerged as powerful tools due their ability replicate tumor microenvironment facilitate preclinical drug development. are simpler 3D culture that partially recreate structure cell interactions. They can be used penetration studies high-throughput screening. Organoids derived from stem cells or patient tissues accurately emulate complexity functionality tissue. generated pluripotent adult cells, well specimens, providing personalized studying behavior responses. retain genetic variability original offer robust platform screening treatment strategies. However, both spheroids limitations, such absence functional vasculature immune components, which essential growth therapeutic The field modeling evolving, with ongoing efforts predictive reflect complexities human cancer. By integrating these tools, researchers gain deeper insights into accelerate novel

Language: Английский

---

Comprehensive multi-omics analyses exposes a precision therapy strategy that targets replication stress in hepatocellular carcinoma using WEE1 inhibition

Journal of Advanced Research, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Language: Английский

---

Anti-EGFR therapy can overcome acquired resistance to the third-generation ALK-tyrosine kinase inhibitor lorlatinib mediated by activation of EGFR

Acta Pharmacologica Sinica, Journal Year: 2025, Volume and Issue: unknown

Published: March 21, 2025

Language: Английский

---

IFN-γ could induce ferroptosis in keloid fibroblasts by inhibiting the expression of serpine2

Cell Death Discovery, Journal Year: 2025, Volume and Issue: 11(1)

Published: May 5, 2025

Abstract Keloids are common pathological scars resulting from previous trauma or inflammation. Interferon-gamma (IFN-γ) has shown significant therapeutic effects when used alone in combination with other agents. While IFN-γ been found to regulate ferroptosis tumor cells, its ability keloid fibroblasts (KFs) is unclear. Here, we have demonstrated a direct causal relationship between levels and KFs. To explore the intrinsic mechanism, performed genome-wide RNA proteomics sequencing that serpine2 was most significantly downregulated gene KFs after exogenous overexpression of IFN-γ. Serpine2, which belongs family serine protease inhibitors, play an important role fibrotic diseases. Therefore, hypothesized downstream regulation by Our results showed promotes collagen synthesis, turn proliferation, migration, invasive functions We further promoted system Xc − transporter expression, cystine uptake, glutathione enhanced GPX4 activity; inhibited reactive oxygen species generation. This resulted reduction intracellular lipid peroxidation metabolite malondialdehyde, as well reversed these overexpression. These were largely confirmed vivo models too. findings imply not only directly induces but also enhances their sensitivity inhibiting synthesis SLC7A11 SLC3A2 through downregulation serpine2. In summary, suggest serpine2-system axis promising target for treatment keloids.

Language: Английский

---

PCBP2-dependent secretion of miRNAs via extracellular vesicles contributes to the EGFR-driven angiogenesis

Theranostics, Journal Year: 2024, Volume and Issue: 15(4), P. 1255 - 1271

Published: Dec. 31, 2024

Rationale:The EGFR-driven angiogenesis is crucial in solid tumors, particularly through the delivery of biomolecules via extracellular vesicles (EVs), but mechanism by which EGFR regulates EV cargo still unclear.Methods: First, cell co-culture and murine tumor models were employed to examine impact overexpression on pro-angiogenic properties small EVs (sEVs) derived from oral squamous carcinoma (OSCC).Small RNA sequencing was then used compare miRNA profiles OSCC-sEVs with without overexpression, followed functional enrichment motif analyses differentially expressed miRNAs.Next, pull-down assays conducted identify potential molecules involved sorting these miRNAs.Finally, role candidate protein validated using existing public database, tissue samples, lines, models.Results: significantly enhances effects OSCC-sEVs, accompanied a marked increase content nucleic acid carried sEVs.Small-RNA identified group miRNAs that enriched due primarily functioned shared characteristic "GGGU" motif.EGFR also strengthened binding PCBP2 containing this motif, thereby promoting their secretion sEVs support angiogenesis.Mechanismly, upregulates activating its transcription rather than regulating mRNA stability OSCC cells.Additionally, depletion impaired inhibiting sEVs.Conclusions: boosts expression transcriptional regulation, promotes loading specific into driving angiogenesis.

Language: Английский

---

LGR4 attenuates MGP expression and suppresses EGFR activation-induced triple-negative breast cancer metastasis

American Journal of Cancer Research, Journal Year: 2024, Volume and Issue: 14(7), P. 3419 - 3432

Published: Jan. 1, 2024

Breast cancer has emerged as the most common globally, with a significant reduction in overall survival rate after metastasis. Compared other types of breast cancer, triple-negative (TNBC) is more prone to metastasize, presenting substantial treatment challenges due lack effective therapies. LGR4, which highly expressed been shown promote proliferation and invasion cells. However, its specific role TNBC remains unclear. In this study, we applied multi-omics approach explore regulatory mechanism LGR4 Our findings showed that could regulate actin cytoskeletal through EGFR curtail activation-induced metastasis by inhibiting MGP expression. These insights provide new perspectives on

Language: Английский

---

Transcriptome Analyses of Liver Sinusoidal Endothelial Cells Reveal a Consistent List of Candidate Genes Associated with Endothelial Dysfunction and the Fibrosis Progression

Current Issues in Molecular Biology, Journal Year: 2024, Volume and Issue: 46(8), P. 7997 - 8014

Published: July 25, 2024

Liver fibrosis is an important step in the transformation of chronic liver disease into cirrhosis and cancer, structural changes functional disorders sinusoidal endothelial cells (LSECs) are early events occurrence fibrosis. Therefore, it necessary to identify key regulatory genes dysfunction process provide a reference for diagnosis treatment In this study, we identified 230 common differentially expressed (Co-DEGs) by analyzing transcriptomic data primary LSECs from three different mouse models (carbon tetrachloride; choline-deficient, l-amino acid-defined diet; nonalcoholic steatohepatitis). Enrichment analysis revealed that Co-DEGs were mainly involved regulating inflammatory response, immune angiogenesis, formation degradation extracellular matrix, mediating chemokine-related pathways. A Venn diagram was used 17 related progression cirrhosis. Regression using Lasso-Cox method prognosis among these genes:

Language: Английский

---