ArticleCancer cell international2022
KRAS acting through ERK signaling stabilizes PD-L1 via inhibiting autophagy pathway in intrahepatic cholangiocarcinoma.
Article in Cancer cell international, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 33 citations in OpenAlex.
- Molecular convergence in gallbladder cancer: MEK-ERK signalling at the crossroads of oncogenic hubs and pathway cross-talks.Cancer cell international · 2026Review
- Investigating PAK inhibition in combination with PD-1 blockade to enhance cytotoxic CD8+ T cell-mediated killing and suppress invasion of ovarian cancer cells.British journal of cancer · 2026Article
- Stratifying cholangiocarcinoma: tumor microenvironment, molecular drivers, and novel immunotherapeutic approaches.Clinical and molecular hepatology · 2026Review
- The role of PD‑1/PD‑L1 axis in liver diseases.Clinical and experimental medicine · 2025Review
- The mechanism and research progress of PD-1/PD-L1 on immune escape of lung cancer.Translational cancer research · 2025Review
- Secreted AZGP1 induced by 5-FU binds to PD-L1 and promotes apoptosis in cholangiocarcinoma.Molecular medicine (Cambridge, Mass.) · 2025Article
- Mechanistic Foundations of KRAS-Driven Tumor Ecosystems: Integrating Crosstalk among Immune, Metabolic, Microbial, and Stromal Microenvironment.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Glucocorticoids Downregulate PD-L1 in Glioblastoma Cells via GILZ-Mediated ERK Inhibition.Biomedicines · 2025Article
- Epigenetic targeting of MECOM/KRAS axis by JIB-04 impairs tumorigenesis and cisplatin resistance in MECOM-amplified ovarian cancer.Cell death discovery · 2025Article
- Precision immune regulation in KRAS-mutated cancers: the final piece of the puzzle?Journal of experimental & clinical cancer research : CR · 2025Review
- ERK1/2 Signaling in Intrahepatic Cholangiocarcinoma: From Preclinical Advances to Therapeutic Strategies.Biology · 2025Review
- Autophagy in cholangiocarcinoma: a comprehensive review about roles and regulatory mechanisms.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025Review
- IL-22/IL-22R1 pathway enhances cholangiocarcinoma progressionWorld journal of gastrointestinal oncology · 2025Article
- ANLN promotes head and neck squamous cell carcinoma progression by upregulating PD-L1 via the ERK-MAPK pathway.iScience · 2025Article
- lncRNA NKILA Promotes Warburg Effect and Immune Escape in Intrahepatic Cholangiocarcinoma by Regulating the MTX1/TOMM40 Axis.Mediators of inflammation · 2025Article
- M2-like Macrophages-derived CCL17 Promotes Esophageal Squamous Cell Carcinoma Metastasis and Stemness via Activating CCR4-mediated ERK/PD-L1 Pathway.Current molecular medicine · 2025Article
- Review
- Exploring the Genomic Landscape of Hepatobiliary Cancers to Establish a Novel Molecular Classification System.Cancers · 2024Article
- Association of Neurokinin-1 Receptor Signaling Pathways with Cancer.Current medicinal chemistry · 2024Review
- Autophagy modulates physiologic and adaptive response in the liver.Liver research (Beijing, China) · 2023Review
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Authors and funding
16 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundWhile the correlation between PD-L1 expression and KRAS mutation has been previously reported in other solid tumors such as non-small cell lung cancer (NSCLC), whether PD-L1 can be modulated by ERK signaling downstream of KRAS in intrahepatic cholangiocarcinoma (iCCA) and the underlying molecular regulatory mechanism remain unclear.
methodsThe expression of ERK, p-ERK, PD-L1 and autophagy markers following KRAS knockdown or Ras/Raf/MEK/ERK signaling inhibitors treatment was examined in two human iCCA cell lines (HuCCT1 and RBE) using western blotting and immunofluorescence. Both pharmacological autophagy inhibitors and short-interfering RNA against ATG7 were applied to inhibit autophagy. The apoptosis rates of iCCA cell lines were detected by flow cytometry and CCK-8 after co-culturing with CD3/CD28-activated human CD8
resultsThe present study demonstrated that the PD-L1 expression level was distinctly reduced in KRAS-mutated iCCA cell lines when ERK signaling was inhibited and ERK phosphorylation levels were lowered. The positive association between p-ERK and PD-L1 was also verified in 92 iCCA tissue samples. Moreover, ERK inhibition induced autophagy activation. Both inhibiting autophagy via autophagy inhibitors and genetically silencing the ATG7 expression partially reversed the reduced PD-L1 expression caused by ERK inhibition. In addition, ERK-mediated down-regulation of PD-L1 via autophagy pathways induced the apoptosis of iCCA cells when co-cultured with CD3/CD28-activated human CD8
conclusionsOur results suggest that ERK signaling inhibition contributes to the reduction of PD-L1 expression through the autophagy pathway in iCCA. As a supplement to anti-PD-1/PD-L1 immunotherapy, ERK-targeted therapy may serve as a potentially novel treatment strategy for human KRAS-mutated iCCA.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.