ArticleExperimental & molecular medicine2020
PROM2 promotes gemcitabine chemoresistance via activating the Akt signaling pathway in pancreatic cancer.
Article in Experimental & molecular medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 45 citations in OpenAlex.
- Prominin 2 promotes the progression of breast cancer by inhibiting ferroptosisJournal of translational internal medicine · 2026Article
- Melatonin augments anti-tumor activity and alleviates nephrotoxicity of gemcitabine in a pancreatic cancer xenograft model targeting P62/Keap1 pathway.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- Nuclear export of transmembrane protein PROM2 is specially regulated by CRM1 and affects the sensitivity of ferroptosis in gastric cancer.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2025Article
- Multi-Omics analysis and in vitro validation reveal diagnostic and therapeutic roles of novel hub genes in ovarian cancer.Hereditas · 2025Article
- SLC5A3 depletion promotes apoptosis by inducing mitochondrial dysfunction and mitophagy in gemcitabine-resistant pancreatic cancer cells.Cell death & disease · 2025Article
- Article
- Clinical application and drug resistance mechanism of gemcitabine.Frontiers in cell and developmental biology · 2025Review
- Inhibition of HOXC11 by artesunate induces ferroptosis and suppresses ovarian cancer progression through transcriptional regulation of the PROM2/PI3K/AKT pathway.World journal of surgical oncology · 2024Article
- Atypical phosphatase DUSP11 inhibition promotes nc886 expression and potentiates gemcitabine-mediated cell death through NF-kB modulation.Cancer gene therapy · 2024Article
- Regulation of tumorigenesis and ferroptosis in non-small cell lung cancer by a novel BBOX1-AS1/miR-326/PROM2 axis.Molecular and cellular biochemistry · 2024Article
- PROM2 overexpression induces metastatic potential through epithelial-to-mesenchymal transition and ferroptosis resistance in human cancers.Clinical and translational medicine · 2024Article
- Prominin 2 decreases cisplatin sensitivity in non-small cell lung cancer and is modulated by CTCC binding factor.Radiology and oncology · 2023Article
- PAK4 inhibition significantly potentiates Gemcitabine activity in PDAC cells via inhibition of Wnt/β-catenin, p-ERK/MAPK and p-AKT/PI3K pathways.Biochemistry and biophysics reports · 2023Article
- The circadian clock is disrupted in pancreatic cancer.PLoS genetics · 2023Article
- A Novel Cuproptosis-Associated Gene Signature to Predict Prognosis in Patients with Pancreatic Cancer.BioMed research international · 2023Article
- Pralatrexate mediates effective killing of gemcitabine-resistant pancreatic cancer: role of mTOR/4E-BP1 signal pathway.Heliyon · 2022Article
- RRP9 promotes gemcitabine resistance in pancreatic cancer via activating AKT signaling pathway.Cell communication and signaling : CCS · 2022Article
- Culprits of PDAC resistance to gemcitabine and immune checkpoint inhibitor: Tumour microenvironment components.Frontiers in molecular biosciences · 2022Review
- Elucidating the mechanism behind and investigating the efficacy of Traditional Chinese Medicine and Traditional Tibetan Medicine in combination with standard therapeutics in hepatocellular carcinoma and cholangiocarcinomaFrontiers in pharmacology · 2022Article
- Noncoding RNAs Associated with Therapeutic Resistance in Pancreatic Cancer.Biomedicines · 2021Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In recent years, the deoxycytidine analogue gemcitabine (2',2',-difluorodeoxycytidine) has become the first-line chemotherapeutic agent for patients with pancreatic cancer. However, due to the intrinsic resistance of pancreatic cancer cells, gemcitabine-based chemotherapy yields limited disease control, with >85% disease progression at 6 months from diagnosis. Therefore, elucidating the mechanisms of chemoresistance is a critical step in improving cancer therapy, especially for the treatment of pancreatic cancer. We show PROM2, a transmembrane glycoprotein, is ubiquitously upregulated in pancreatic cancer cell. We also found higher PROM2 expression is associated with shortened overall and disease-free survival times in patients diagnosed with pancreatic cancer. We provide evidence that PROM2 promotes chemoresistance to gemcitabine both in vivo and in vitro. Mechanistically, we demonstrate that PROM2 could directly interacted with Akt and activates the Akt signaling pathway, which thus inhibiting gemcitabine-induced apoptosis. As further evidence, we show PROM2 expression and Akt phosphorylation both promote gemcitabine chemoresistance, and cause poorer survival in clinical samples with pancreatic cancer. Combining gemcitabine with the Akt inhibitor MK-2206 facilitated significant tumor shrinkage and dramatically elevated the survival status in mice xenografted with pancreatic cancer cells. Our findings not only establish PROM2 as a novel positive regulator of the Akt signaling pathway and a candidate prognostic indicator of gemcitabine response, but also provide a neo-therapeutic approach for patients resistant to gemcitabine treatment.
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