ArticleAutophagy2015
Loss of STK11 expression is an early event in prostate carcinogenesis and predicts therapeutic response to targeted therapy against MAPK/p38.
Article in Autophagy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
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The trial behind it
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Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 45 citations in OpenAlex.
- Recent advances in the molecular targeted drugs for prostate cancer.International urology and nephrology · 2023Pooled it
- Review
- The role of autophagy in prostate cancer and prostatic diseases: a new therapeutic strategy.Prostate cancer and prostatic diseases · 2024Review
- Pharmacological agents targeting drug-tolerant persister cells in cancer.Pharmacological research · 2024Review
- Ischemia-Reperfusion Injury in Kidney Transplantation: Mechanisms and Potential Therapeutic Targets.International journal of molecular sciences · 2024Review
- Impact of sunitinib resistance on clear cell renal cell carcinoma therapeutic sensitivityCell cycle (Georgetown, Tex.) · 2024Article
- Therapy resistance in prostate cancer: mechanism, signaling and reversal strategies.Exploration of targeted anti-tumor therapy · 2024Review
- Cancer Stem Cells in Renal Cell Carcinoma: Origins and Biomarkers.International journal of molecular sciences · 2023Review
- Cellular and Molecular Players in the Tumor Microenvironment of Renal Cell Carcinoma.Journal of clinical medicine · 2023Review
- Autophagy: A challengeable paradox in cancer treatment.Cancer medicine · 2023Review
- Mechanisms of Prostate Cancer Cells Survival and Their Therapeutic Targeting.International journal of molecular sciences · 2023Review
- Emerging Hallmarks of Metabolic Reprogramming in Prostate Cancer.International journal of molecular sciences · 2023Review
- Targeting Glutamine Metabolism in Prostate Cancer.Frontiers in bioscience (Elite edition) · 2023Review
- AMPK's double-faced role in advanced stages of prostate cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2022Review
- Novel Insights into Autophagy and Prostate Cancer: A Comprehensive Review.International journal of molecular sciences · 2022Review
- Lavender protects H9c2 cardiomyocytes against oxygen-glucose deprivation (OGD)-induced injury via targeting the JAK2/STAT3 pathway.Iranian journal of basic medical sciences · 2022Article
- Prostate Cancer Radiogenomics-From Imaging to Molecular Characterization.International journal of molecular sciences · 2021Review
- p38β - MAPK11 and its role in female cancers.Journal of ovarian research · 2021Review
- Integration of Lipidomics and Transcriptomics Reveals Reprogramming of the Lipid Metabolism and Composition in Clear Cell Renal Cell Carcinoma.Metabolites · 2020Article
- p38β and Cancer: The Beginning of the Road.International journal of molecular sciences · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
20 authors at 5 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Prostate cancer (PCa) is the second leading cause of cancer-related death in men; however, the molecular mechanisms leading to its development and progression are not yet fully elucidated. Of note, it has been recently shown that conditional stk11 knockout mice develop atypical hyperplasia and prostate intraepithelial neoplasia (PIN). We recently reported an inverse correlation between the activity of the STK11/AMPK pathway and the MAPK/p38 cascade in HIF1A-dependent malignancies. Furthermore, MAPK/p38 overactivation was detected in benign prostate hyperplasia, PIN and PCa in mice and humans. Here we report that STK11 expression is significantly decreased in PCa compared to normal tissues. Moreover, STK11 protein levels decreased throughout prostate carcinogenesis. To gain insight into the role of STK11-MAPK/p38 activity balance in PCa, we treated PCa cell lines and primary biopsies with a well-established MAPK14-MAPK11 inhibitor (SB202190), which has been extensively used in vitro and in vivo. Our results indicate that inhibition of MAPK/p38 significantly affects PCa cell survival in an STK11-dependent manner. Indeed, we found that pharmacologic inactivation of MAPK/p38 does not affect viability of STK11-proficient PCa cells due to the triggering of the AMPK-dependent autophagic pathway, while it induces apoptosis in STK11-deficient cells irrespective of androgen receptor (AR) status. Of note, AMPK inactivation or autophagy inhibition in STK11-proficient cells sensitize SB202190-treated PCa cells to apoptosis. On the other end, reconstitution of functional STK11 in STK11-deficient PCa cells abrogates apoptosis. Collectively, our data show that STK11 is a key factor involved in the early phases of prostate carcinogenesis, and suggest that it might be used as a predictive marker of therapeutic response to MAPK/p38 inhibitors in PCa patients.
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Registered trials
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.