Current view of liver cancer cell-of-origin and proposed mechanisms precluding its proper determination DOI Creative Commons
Tomasz Gromowski, Veronika Lukacs‐Kornek,

Jarosław Cisowski

et al.

Cancer Cell International, Journal Year: 2023, Volume and Issue: 23(1)

Published: Jan. 6, 2023

Abstract Hepatocellular carcinoma and intrahepatic cholangiocarcinoma are devastating primary liver cancers with increasing prevalence in many parts of the world. Despite intense investigation, aspects their biology still largely obscure. For example, numerous studies have tackled question cell-of-origin using different experimental approaches; they not, however, provided a clear undisputed answer. Here, we will review evidence from animal models supporting role all major types epithelial cells: hepatocytes, cholangiocytes, common progenitor as cancer cell-of-origin. Moreover, also propose mechanisms that promote cell plasticity (dedifferentiation, transdifferentiation, epithelial-to-mesenchymal transition) which may contribute to misinterpretation results make issue particularly complex.

Language: Английский

Fibroblast and myofibroblast activation in normal tissue repair and fibrosis DOI
Fereshteh S. Younesi, Andrew Miller, Thomas H. Barker

et al.

Nature Reviews Molecular Cell Biology, Journal Year: 2024, Volume and Issue: 25(8), P. 617 - 638

Published: April 8, 2024

Language: Английский

Citations

152
Insights into recent findings and clinical application of YAP and TAZ in cancer DOI
James Franklin, ZhengMing Wu, Kun‐Liang Guan

et al.

Nature reviews. Cancer, Journal Year: 2023, Volume and Issue: 23(8), P. 512 - 525

Published: June 12, 2023

Language: Английский

Citations

113
Notch signaling pathway in cancer: from mechanistic insights to targeted therapies DOI Creative Commons

Qingmiao Shi,

Chen Xue,

Yifan Zeng

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: May 27, 2024

Notch signaling, renowned for its role in regulating cell fate, organ development, and tissue homeostasis across metazoans, is highly conserved throughout evolution. The receptor ligands are transmembrane proteins containing epidermal growth factor-like repeat sequences, typically necessitating receptor-ligand interaction to initiate classical signaling transduction. Accumulating evidence indicates that the pathway serves as both an oncogenic factor a tumor suppressor various cancer types. Dysregulation of this promotes epithelial-mesenchymal transition angiogenesis malignancies, closely linked proliferation, invasion, metastasis. Furthermore, contributes maintaining stem-like properties cells, thereby enhancing invasiveness. regulatory metabolic reprogramming microenvironment suggests pivotal involvement balancing suppressive effects. Moreover, implicated conferring chemoresistance cells. Therefore, comprehensive understanding these biological processes crucial developing innovative therapeutic strategies targeting signaling. This review focuses on research progress cancers, providing in-depth insights into potential mechanisms regulation occurrence progression cancer. Additionally, summarizes pharmaceutical clinical trials therapy, aiming offer new human malignancies.

Language: Английский

Citations

97
Loss of liver function in chronic liver disease: An identity crisis DOI Creative Commons
Carmen Berasain, María Arechederra, Josepmaría Argemí

et al.

Journal of Hepatology, Journal Year: 2022, Volume and Issue: 78(2), P. 401 - 414

Published: Sept. 15, 2022

Adult hepatocyte identity is constructed throughout embryonic development and fine-tuned after birth. A multinodular network of transcription factors, along with pre-mRNA splicing regulators, define the transcriptome, which encodes proteins needed to perform complex metabolic secretory functions mature liver. Transient hepatocellular dedifferentiation can occur as part regenerative mechanisms triggered in response acute liver injury. However, persistent downregulation key genes now accepted a strong determinant organ dysfunction chronic disease, major global health burden. Therefore, identification core factors regulators that preserve phenotype, thorough understanding how these networks become disrupted diseased hepatocytes, high clinical relevance. In this context, we review players differentiation discuss detail critical such HNF4α, whose impairment mediates breakdown function. Moreover, present compelling experimental evidence demonstrating restoration factor expression chronically injured reset identity, improve function ameliorate structural abnormalities. The possibility correcting phenotype severely damaged malfunctional livers may reveal new therapeutic opportunities for individuals cirrhosis advanced disease.

Language: Английский

Citations

56
HNF4α inhibits the malignancy of intrahepatic cholangiocarcinoma by suppressing the Wnt signaling pathway DOI
Binghe Xu, Chenbo Ding, Yilong Liu

et al.

Translational Oncology, Journal Year: 2025, Volume and Issue: 53, P. 102290 - 102290

Published: Jan. 25, 2025

Language: Английский

Citations

1
NELL2 suppresses epithelial-mesenchymal transition and induces ferroptosis via notch signaling pathway in HCC DOI Creative Commons
Shiqi Liu, Haomin Wu, Pengjie Zhang

et al.

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: March 25, 2025

Although various malignant tumors have been associated with the aberrant expression of Neural Epidermal Growth Factor-Like 2 (NELL2), its involvement in hepatocellular carcinoma (HCC) has not previously documented. In this study, NELL2, recognized as a crucial tumor-suppressor gene, was found to be infrequently expressed HCC. vitro experiments demonstrated that overexpression NELL2 significantly inhibited proliferation, migration, and invasion liver cancer cells, whereas suppression markedly enhanced these oncogenic properties. Further investigation revealed impedes epithelial-mesenchymal transition (EMT) via Notch signaling pathway. Inhibition pathway reversed increased tumor observed following downregulation expression. Notably, gene enrichment analysis studies indicated effectively induced ferroptosis HCC evidenced by levels cellular malondialdehyde (MDA), iron, Reactive Oxygen Species (ROS), alongside decreased glutathione (GSH) levels. The blockade substantially diminished NELL2's capacity induce ferroptosis. summary, our findings suggest modulates inhibit EMT promote Consequently, may serve novel therapeutic target, potentially functioning suppressor

Language: Английский

Citations

1
Helicobacter pylori-induced aberrant demethylation and expression of GNB4 promotes gastric carcinogenesis via the Hippo–YAP1 pathway DOI Creative Commons
Duanrui Liu, Yunyun Liu,

Wenshuai Zhu

et al.

BMC Medicine, Journal Year: 2023, Volume and Issue: 21(1)

Published: April 5, 2023

Helicobacter pylori (H. pylori) infection causes aberrant DNA methylation and contributes to the risk of gastric cancer (GC). Guanine nucleotide-binding protein subunit beta-4 (GNB4) is involved in various tumorigenic processes. We found an level GNB4 H. pylori-induced GC our previous bioinformatic analysis; however, its expression underlying molecular mechanisms are poorly understood.The expression, signaling pathways, clinical significance were analyzed a local cohort 107 patients with several public databases. was induced vitro vivo models. Methylation-specific PCR, pyrosequencing, mass spectrometry analysis used detect changes levels. GNB4, TET1, YAP1 overexpressed or knocked down cell lines. performed gain- loss-of-function experiments, including CCK-8, EdU, colony formation, transwell migration, invasion assays. Nude mice injected genetically manipulated cells, growth xenograft tumors metastases measured. Real-time quantitative western blotting, immunofluorescence, immunohistochemistry, chromatin immunoprecipitation, co-immunoprecipitation experiments elucidate mechanisms.GNB4 significantly upregulated correlated aggressive characteristics poor prognosis. Increased levels associated shorter survival times. Infection strains 26695 SS1 mRNA lines mice. Additionally, silencing blocked pro-proliferative, metastatic, invasive ability cells. remarkably decreased promoter region, particularly at CpG#5 site (chr3:179451746-179451745). TET1 via activation NF-κB. TET binds region which undergoes demethylation modification. Functionally, we identified that oncogenic behaviors Hippo-YAP1 pathway both models.Our findings demonstrate activates NF-κB-TET1-GNB4 demethylation-YAP1 axis, may be potential therapeutic target for GC.

Language: Английский

Citations

19
Hydrodynamic Delivery: Characteristics, Applications, and Technological Advances DOI Creative Commons
Takeshi Suda, Takeshi Yokoo,

Tsutomu Kanefuji

et al.

Pharmaceutics, Journal Year: 2023, Volume and Issue: 15(4), P. 1111 - 1111

Published: March 31, 2023

The principle of hydrodynamic delivery was initially used to develop a method for the plasmids into mouse hepatocytes through tail vein injection and has been expanded use in various biologically active materials cells organs variety animal species systemic or local injection, resulting significant advances new applications technological development. development regional directly supports successful gene large animals, including humans. This review summarizes fundamentals progress that made its application. Recent this field offers tantalizing prospects generation technologies broader application delivery.

Language: Английский

Citations

18
Emerging Therapies in Management of Cholangiocarcinoma DOI Open Access

Jessica Speckart,

Veronica Rasmusen,

Zohray Talib

et al.

Cancers, Journal Year: 2024, Volume and Issue: 16(3), P. 613 - 613

Published: Jan. 31, 2024

Cholangiocarcinoma is a heterogeneous group of biliary tract cancers that has poor prognosis and globally increasing incidence mortality. While surgical resection remains the only curative option for treatment cholangiocarcinoma, majority are unresectable at time diagnosis. Additionally, cholangiocarcinoma even with current first-line systemic therapy regimens, highlighting difficulty treating locally advanced, metastatic, or cholangiocarcinoma. Through recent developments, targetable oncogenic driver mutations have been identified in pathogenesis leading to utilization molecular targeted therapeutics. In this review, we comprehensively discuss latest therapeutics including emerging immunotherapies, promising developments strategies.

Language: Английский

Citations

7
FABP5+ lipid-loaded macrophages process tumor-derived unsaturated fatty acid signal to suppress T-cell antitumor immunity DOI
Xuguang Yang, Bo Deng, Weiwei Zhao

et al.

Journal of Hepatology, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 1, 2024

Language: Английский

Citations

6