GRP78 inhibitor YUM70 upregulates 4E-BP1 and suppresses c-MYC expression and viability of oncogenic c-MYC tumors DOI Creative Commons
Vicky Yamamoto, Dat P. Ha, Ze Liu

et al.

Neoplasia, Journal Year: 2024, Volume and Issue: 55, P. 101020 - 101020

Published: July 10, 2024

The 78-kDa glucose regulated protein (GRP78) commonly upregulated in a wide variety of tumors is an important prognostic marker and promising target for suppressing tumorigenesis treatment resistance. While GRP78 well established as major endoplasmic reticulum (ER) chaperone with anti-apoptotic properties master regulator the unfolded response, its new role oncoprotein expression just emerging. MYC dysregulated about 70 % human cancers most activated oncoprotein. However, despite recent advances, therapeutic targeting remains challenging. Here we identify suppression expression. Using multiple MYC-dependent cancer models including head neck squamous cell carcinoma their cisplatin-resistant clones, breast pancreatic adenocarcinoma, our studies revealed that knockdown by siRNA or inhibition activity small molecule inhibitors (YUM70 HA15) reduced c-MYC expression, leading to onset apoptosis loss viability. This was observed 2D culture, 3D spheroid xenograft models. Mechanistically, determined at post-transcriptional level YUM70 HA15 potently eukaryotic translation inhibitor 4E-BP1, which targets eIF4E critical initiation. Furthermore, knock-down 4E-BP1 via rescued YUM70-mediated suppression. As also capable N-MYC this study offers approach suppress through GRP78.

Language: Английский

Tumor energy metabolism: implications for therapeutic targets DOI Creative Commons

Youwu Hu,

Wanqing Liu,

WanDi Fang

et al.

Molecular Biomedicine, Journal Year: 2024, Volume and Issue: 5(1)

Published: Nov. 29, 2024

Abstract Tumor energy metabolism plays a crucial role in the occurrence, progression, and drug resistance of tumors. The study tumor has gradually become an emerging field treatment. Recent studies have shown that epigenetic regulation is closely linked to metabolism, influencing metabolic remodeling biological traits cells. This review focuses on primary pathways explores therapeutic strategies target these pathways. It covers key areas such as glycolysis, Warburg effect, mitochondrial function, oxidative phosphorylation, adaptability Additionally, this article examines regulator SWI/SNF complex specifically its interactions with glucose, lipids, amino acids. Summarizing aimed at pathways, including inhibitors mitochondrial-targeted drugs, exploitation vulnerabilities, recent developments related complexes potential targets. clinical significance, challenges, future directions research are discussed, overcome resistance, combination therapy, application new technologies.

Language: Английский

Citations

7
Leveraging Epigenetic Alterations in Pancreatic Ductal Adenocarcinoma for Clinical Applications DOI Creative Commons
Jörg Tost,

Secil Ak-Aksoy,

Daniele Campa

et al.

Seminars in Cancer Biology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

Citations

0
The Crosstalk between Nerves and Cancer—A Poorly Understood Phenomenon and New Possibilities DOI Open Access

David Benzaquen,

Yaacov Richard Lawrence,

Daniel Taussky

et al.

Cancers, Journal Year: 2024, Volume and Issue: 16(10), P. 1875 - 1875

Published: May 15, 2024

Introduction: Crosstalk occurs between nerve and cancer cells. These interactions are important for homeostasis metabolism. Nerve cells influence the tumor microenvironment (TME) participate in metastasis through neurogenesis, neural extension, axonogenesis. We summarized past current literature on interaction nerves cancer, with a special focus pancreatic ductal adenocarcinoma (PDAC), prostate (PCa), role of growth factor (NGF) cancer. Materials/Methods: reviewed PubMed Google Scholar relevant relationship nerves, neurotrophins, general specifically both PCa PDAC. Results: The NGF helped sustain cell proliferation evade immune defense. It is neuropeptide involved neurogenic inflammation activation several system by proinflammatory cytokines. Both PDAC employ different strategies to richly innervated sympathetic parasympathetic which helps control homeostasis. Newly formed autonomic fibers grow into contribute initiation progression β-adrenergic muscarinic cholinergic signaling. Surgical or chemical sympathectomy prevents development Beta-blockers have high therapeutic potential although clinical data been contradictory. With better understanding beta-receptors, one could identify specific receptors that an effect act as agents. Conclusion: bidirectional crosstalk nervous has emerged crucial regulator its microenvironment. Denervation shown be promising vitro animal models. Additionally, there psychosocial biology neurotransmitters neurotrophins.

Language: Английский

Citations

2
GRP78 inhibitor YUM70 upregulates 4E-BP1 and suppresses c-MYC expression and viability of oncogenic c-MYC tumors DOI Creative Commons
Vicky Yamamoto, Dat P. Ha, Ze Liu

et al.

Neoplasia, Journal Year: 2024, Volume and Issue: 55, P. 101020 - 101020

Published: July 10, 2024

The 78-kDa glucose regulated protein (GRP78) commonly upregulated in a wide variety of tumors is an important prognostic marker and promising target for suppressing tumorigenesis treatment resistance. While GRP78 well established as major endoplasmic reticulum (ER) chaperone with anti-apoptotic properties master regulator the unfolded response, its new role oncoprotein expression just emerging. MYC dysregulated about 70 % human cancers most activated oncoprotein. However, despite recent advances, therapeutic targeting remains challenging. Here we identify suppression expression. Using multiple MYC-dependent cancer models including head neck squamous cell carcinoma their cisplatin-resistant clones, breast pancreatic adenocarcinoma, our studies revealed that knockdown by siRNA or inhibition activity small molecule inhibitors (YUM70 HA15) reduced c-MYC expression, leading to onset apoptosis loss viability. This was observed 2D culture, 3D spheroid xenograft models. Mechanistically, determined at post-transcriptional level YUM70 HA15 potently eukaryotic translation inhibitor 4E-BP1, which targets eIF4E critical initiation. Furthermore, knock-down 4E-BP1 via rescued YUM70-mediated suppression. As also capable N-MYC this study offers approach suppress through GRP78.

Language: Английский

Citations

0