Human epidermal growth factor receptor 2 (HER-2), a famous therapeutic target for breast cancer, is also associated with an increased risk of recurrence and poor outcomes of other malignancies, including gastric cancer. Yet the mechanism of HER-2 therapy resistance remains controversial due to the heterogeneity of gastric adenocarcinoma. We know, Procollagen-Lysine,2-Oxoglutarate 5-Dioxygenase 3 (PLOD3), a key gene coding enzymes that catalyze the lysyl hydroxylation of extracellular matrix collagen, plays an important contributor to HER-2 targeting agent Trastuzumab resistance in gastric cancer. Herein, we analyzed clinical samples of gastric cancer patients and gastric cancer cell lines and identified PLOD3, unveiled that depletion of PLOD3 leads to decreased cell proliferation, tumor growth and Trastuzumab sensitivity in these Trastuzumab resistant GC cell lines. Clinically, increased PLOD3 expression correlates with decreased Trastuzumab therapy responsiveness in GC patients. Mechanistically, we show that PLOD3 represses tumor suppressor FoxO3 expression, therefore upregulating Survivin protein expression that contributes to Trastuzumab resistance in GC. Therefore, our study identifies a new signaling axis PLOD3-FoxO3- Survivin pathway that may be therapeutically targeted in HER-2 positive gastric cancer.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9283410 | PMC |
| http://dx.doi.org/10.1038/s41420-022-01103-4 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Exploring the expression of DLL3 in gastroenteropancreatic neuroendocrine neoplasms and its potential diagnostic value.
Sci Rep
January 2025
State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Department of Pathology, Peking University Cancer Hospital and Institute, 52 Fucheng Road, Haidian District, Beijing, 100142, China.
Delta-like protein (DLL3) is a novel therapeutic target. DLL3 expression in gastroenteropancreatic neuroendocrine tumors (GEP-NECs) is poorly understood, complicating the distinction between well-differentiated neuroendocrine tumors G3 (NET G3) and poorly differentiated NEC. DLL3 immunohistochemistry (IHC) was performed on 248 primary GEP-NECs, correlating with clinicopathological parameters, NE markers, PD-L1, Ki67 index, and prognosis.
View Article and Find Full Text PDFActivation of P38 MAPK Signaling Cascade is Linked with Clinical Outcomes and Therapeutic Responses in Human Cancers.
Biochemistry (Mosc)
December 2024
Moscow Institute of Physics and Technology, Dolgoprudny, 141701, Russia.
Activation of the p38 mitogen-activated protein kinase (MAPK) pathways is vital in regulating cell growth, differentiation, apoptosis, and stress response, significantly affecting tumorigenesis and cancer progression. We developed a bioinformatic technique to construct an interactome network-based molecular pathways for genes of interest and quantify their activation levels using high-throughput gene expression data. This study is focused on the p38α, p38β, p38γ, and p38δ kinases, examining their activation levels (PALs) based on transcriptomic data and their associations with survival and drug responsiveness across various cancer types.
View Article and Find Full Text PDFAcquired vulnerability against EGF receptor inhibition in gastric cancer promoted by class I histone deacetylase inhibitor entinostat.
Neoplasia
January 2025
Leipzig University, Medical Faculty, Rudolf-Boehm-Institute for Pharmacology and Toxicology, Clinical Pharmacology, Leipzig, Germany; Comprehensive Cancer Center Central Germany (CCCG), Leipzig and Jena. Electronic address:
Introduction: Histone deacetylase inhibitors (HDACi) have shown promising preclinical activity in gastric cancer cells; unfortunately, however, these could not be confirmed in clinical trials. This highlights the need for the identification of underlying reasons, which may also provide the basis for possible combination therapies. Here, we delineated the effects of HDACi on components of EGFR signalling in gastric cancer cells.
View Article and Find Full Text PDFMOSPD1 facilitates fatty acid metabolism and gastric cancer progression by promoting the MAPK pathway.
Tissue Cell
January 2025
Department of Gastrointestinal Surgery, The Affiliated Taian City Central Hospital of Qingdao University, Tai'an, Shandong 271000, China. Electronic address:
Background: Motile sperm domain containing 1 (MOSPD1) is overexpressed in colorectal, prostate, and breast cancers, but its role in gastric cancer (GC) progression remains unclear.
Methods: The effect of MOSPD1 was evaluated using cell viability, colony formation, wound healing, and Transwell assays. Triglyceride and lipid levels were measured in GC cells.
Novel nutrition strategies in gastric and esophageal cancer.
Expert Rev Gastroenterol Hepatol
January 2025
Department of Surgery, Trinity St. James's Cancer Institute, Dublin, Ireland.
Introduction: Advances in treatment strategies for gastric and esophageal cancer have led to improved long-term outcomes, however the local and systemic effects of tumor growth, neoadjuvant therapies and surgery, results in specific nutritional challenges. Comprehensive nutritional evaluation and support represents a core component of multidisciplinary holistic care for this patient population.
Areas Covered: This review provides a detailed overview of the nutritional challenges in gastric and esophageal cancer, with a focus on malignant obstruction, preoperative optimization and nutrition in survivorship.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!