A cigarette compound-induced tumor microenvironment promotes sorafenib resistance in hepatocellular carcinoma via the 14-3-3η-modified tumor-associated proteome
Targeting tumor-associated proteomic modifications: Uncovering key pathways in cigarette compound-induced drug resistance via 14-3-3η
2026-01-22
(Press-News.org)
A research team led by Professor Yuan Li at Nanjing Medical University published a research paper entitled "A Cigarette Compound-Induced Tumor Microenvironment Promotes Sorafenib Resistance in Hepatocellular Carcinoma via the 14-3-3η-Modified Tumor-Associated Proteome" in the Chinese Medical Journal. This work provides valuable insights into the role of smoking in HCC progression and drug resistance, offering potential therapeutic targets for overcoming sorafenib resistance.
The study began with an analysis of clinical follow-up data from HCC patients, revealing that smokers exhibited significantly poorer survival outcomes compared to non-smokers. Building on this finding, a sorafenib-resistant HCC cell model induced by cigarette smoking extract (CSE) was established. These results indicate that cigarette compound exposure continuously activates 14-3-3η via epigenetic accumulation of DNA demethylation, and that, the expression level/promoter methylation degree of 14-3-3η influenced the efficacy of sorafenib. Sorafenib plays a pluripotent role mainly by regulating the phosphorylation of multiple-targeted tyrosine kinases and mitigating angiogenesis. By integrating findings from phospho-antibody and angiogenesis antibody arrays, the authors revealed that 14-3-3η activates the B-Raf/ERK signaling pathway and regulates a cascade of downstream factors. This activation enhances anti-apoptotic mechanisms, accelerates drug efflux, and promotes neo-angiogenesis, and these three critical processes synergistically contribute to the development of sorafenib resistance in HCC. Finally, in a subcutaneous tumour xenograft model using nude mice, authors further investigated the expression levels of the aforementioned key molecules and evaluated the therapeutic efficacy of arsenic trioxide (ATO). The results demonstrated that ATO monotherapy significantly suppressed 14-3-3η and its downstream targets, while also inhibiting angiogenesis and promoting apoptosis. Notably, the combination of ATO and sorafenib exhibited a synergistic effect, leading to an even more pronounced suppression of tumor progression.
In this study, we systematically elucidated the key molecular mechanisms underlying sorafenib resistance in HCC induced by chronic smoking exposure, as well as the associated regulatory biological processes. Furthermore, we explored the potential therapeutic effects of traditional Chinese medicine components targeting these critical pathways. The findings not only deepen the theoretical understanding of drug resistance mechanisms in HCC but also provide a robust scientific foundation and practical guidance for optimizing strategies to prevent and control malignant tumors. Additionally, this research opens new avenues for the clinical prevention and treatment of HCC, offering promising applications for future therapeutic interventions.
***
Reference
DOI: https://doi.org/10.1097/CM9.0000000000003851
About Yuan Li from Nanjing Medical University
Yuan Li, PhD, Professor, Doctoral Supervisor. Member of Biomarker Committee of Chinese Society of Environmental Mutagens, and a member of the Chinese Medicine Pharmacology Committee of Jiangsu Pharmacology Society. Main research area: Mechanisms of chronic liver disease process and precise prevention/intervention.
Funding information
This work was supported by grants from the National Natural Science Foundation of China (Nos. 81961160708 and 82270653), the Major Projects of Science and Technology Development Fund of Nanjing Medical University (No. NMUD2019008), the Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD), Jiangsu Provincial Medical Youth Talent (No. QNRC2016672), the Public Welfare Application Research Program of Huzhou (Nos. 2023GZ85 and 2021GY32), the Graduate Research and Innovation Projects of Jiangsu Province (No. KYCX22-1812), the High-Level Talents Research Start-Up Project of Fujian Medical University (No. XRCZX2024032), and the young and middle-aged teacher education research project of Fujian Province (No. JAT241033).
END
ELSE PRESS RELEASES FROM THIS DATE:
2026-01-22
Neurodegenerative diseases such as Alzheimer’s, Parkinson’s, Huntington’s, and amyotrophic lateral sclerosis (ALS) affect millions of people worldwide, yet treatments remain largely limited to symptom management. A defining feature shared by these conditions is the buildup of misfolded proteins that damage neurons over time. Cells normally rely on a protein quality-control system to prevent this damage. At the center of this system are molecular chaperones or heat shock proteins, which help proteins fold correctly or direct misfolded proteins to degradation and helps maintain proteostasis. Among them, the Hsp70 family has attracted growing attention for ...
2026-01-22
The vision of a fully connected world is rapidly becoming a reality through the Internet of Things (IoT)—a growing network of physical devices that collect and share data over the Internet, including everything from small sensors to autonomous vehicles and industrial equipment. To ensure this data is secure and not tampered with, engineers are increasingly turning to blockchain as a promising solution. While often associated with cryptocurrencies, blockchain is essentially a decentralized digital ledger; instead of one company controlling the data, it is shared and maintained collectively across a network of computers.
Unfortunately, ...
2026-01-22
Chemotherapy commonly damages the intestinal lining, a well-known side effect. But this injury does not remain confined to the gut. It reshapes nutrient availability for intestinal bacteria, forcing the microbiota to adapt.
The researchers report that chemotherapy-induced damage to the intestinal lining alters nutrient availability for gut bacteria, reshaping the microbiota and increasing the production of indole-3-propionic acid (IPA), a tryptophan-derived microbial metabolite.
Rather than acting locally, IPA functions as a systemic messenger. It travels from the gut to the ...
2026-01-22
Microorganisms live in biofilms - the equivalent of microbial “cities”- everywhere on Earth. These city-like structures protect and house microbial communities and play essential roles in enabling human and plant health on our planet. Now, a new Perspective article published in npj Biofilms and Microbiomes sets out a path to uncover the role of biofilms in health during long-duration spaceflight, and how spaceflight research can reshape our understanding of these microbial communities on Earth.
Led by researchers at the University of Glasgow in Scotland and Maynooth University and University College Dublin (UCD) in Ireland working within the GeneLab Microbes Analysis ...
2026-01-22
Organic matter carried in rivers to the Russian part of the Arctic Ocean may be creating more clouds and keeping the region cooler, a new study has found.
In a new paper published in Communications Earth & Environment, an international team of researchers, including atmospheric specialists from the University of Birmingham, examined an understudied region of the Arctic Circle which includes the Siberian region of Russia, to understand how aerosol formation, which is essential for cloud formation, was influenced by conditions in the region.
The researchers investigated the origins of Arctic clouds, finding that organic ...
2026-01-22
This preclinical study explains the mechanism underlying CDK2 and CDK4/6 combination therapy, providing a blueprint for future clinical use
These findings are notable because several CDK2 inhibitor candidates are currently making their way to clinical trials
This combination treatment targets two types of breast cancer that currently have limited treatment options
HOUSTON, JANUARY 22, 2026 ― A new preclinical study from researchers at The University of Texas MD Anderson Cancer Center, published today in Nature Communications, ...
2026-01-22
Living walls – structures housing flowers and plants fitted to the outside of new and old buildings – can significantly enhance the biodiversity within urban environments, a new study has shown.
The research monitored activity involving pollinating insects, spiders, soil invertebrates, birds and bats at three locations spread across the city centre and outskirts of Plymouth.
Over three survey periods, hundreds of creatures were observed including 12 different types of bees, hoverflies and other pollinators as well 19 types of soil invertebrates and 12 species of spiders.
There were also 32 bird species recorded across the locations, with three ...
2026-01-22
Enzymes with specific functions are becoming increasingly important in industry, medicine and environmental protection. For example, they make it possible to synthesise chemicals in a more environmentally friendly way, produce active ingredients in a targeted manner or break down environmentally harmful substances. Researchers from Gustav Oberdorfer’s working group at the Institute of Biochemistry at Graz University of Technology (TU Graz), together with colleagues from the University of Graz, ...
2026-01-22
Smartwatches with both PPG and ECG functionality improve the detection of atrial fibrillation in comparison with standard care. Researchers from Amsterdam UMC analysed the data from 437 patients and detected heart arrythmia four times more often in those who wore an Apple Watch. These results are published today in JACC (Journal of the American College of Cardiology).
"Traditionally, monitoring takes place with other ECG devices, but patients can find them a bit irritating, and most of them can only monitor for two weeks at a time,” says Michiel Winter, ...
2026-01-22
A single enzyme that can generate all four nucleotide triphosphates, the building blocks of ribonucleic acid (RNA), was identified by researchers at the Institute of Science Tokyo. By using polyphosphate as a phosphate donor, the enzyme efficiently converts inexpensive nucleotide precursors into the active forms required for RNA synthesis. Overall, the method dramatically simplifies the process of nucleotide production—offering a low-cost, efficient option for the in vitro synthesis of RNA.
All living systems depend on specific biomolecules that form the basic units of life. ...
LAST 30 PRESS RELEASES:
[Press-News.org] A cigarette compound-induced tumor microenvironment promotes sorafenib resistance in hepatocellular carcinoma via the 14-3-3η-modified tumor-associated proteome
Targeting tumor-associated proteomic modifications: Uncovering key pathways in cigarette compound-induced drug resistance via 14-3-3η
