ArticleThe Journal of clinical investigation2019
RABL6A inhibits tumor-suppressive PP2A/AKT signaling to drive pancreatic neuroendocrine tumor growth.
Article in The Journal of clinical investigation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
24 citing papers in PubMed, 36 citations in OpenAlex.
- Development of a Cre-Inducible Rabl6a Transgenic Mouse Model That Enhances Sarcoma Growth In Vivo.Cancers · 2026Article
- Novel Therapeutics and the Path Toward Effective Immunotherapy in Malignant Peripheral Nerve Sheath Tumors.Cancers · 2025Review
- Elucidation of roles of serine/threonine phosphatases PP1 and PP2A in mediating CCK-stimulated growth and enzyme secretion in pancreatic acinar cells.American journal of physiology. Gastrointestinal and liver physiology · 2025Article
- RAB3B Dictates mTORC1/S6 Signaling in Chordoma and Predicts Response to mTORC1-Targeted Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- WDR12/RAC1 axis promoted proliferation and anti-apoptosis in colorectal cancer cells.Molecular and cellular biochemistry · 2024Article
- Integrated stress response plasticity governs normal cell adaptation to chronic stress via the PP2A-TFE3-ATF4 pathway.Cell death and differentiation · 2024Article
- Nicotine-induced activation of cholinergic receptor nicotinic alpha 5 subunit mediates the malignant behaviours of laryngeal squamous epithelial cells by interacting with RABL6.Cell death discovery · 2024Article
- Integrated stress response plasticity governs normal cell adaptation to chronic stress via the PP2A-TFE3-ATF4 pathway.Research square · 2024Article
- Hyperphosphorylation of BCL-2 family proteins underlies functional resistance to venetoclax in lymphoid malignancies.The Journal of clinical investigation · 2023Article
- The oncogenic potential of Rab-like protein 1A (RBEL1A) GTPase: The first review of RBEL1A research with future research directions and challenges.Journal of Cancer · 2023Review
- Intracellular antibody targeting HBx suppresses invasion and metastasis in hepatitis B virus-related hepatocarcinogenesis via protein phosphatase 2A-B56γ-mediated dephosphorylation of protein kinase B.Cell proliferation · 2022Article
- The Role of CDK Pathway Dysregulation and Its Therapeutic Potential in Soft Tissue Sarcoma.Cancers · 2022Review
- Aloperine inhibits the progression of non-small-cell lung cancer through the PI3K/Akt signaling pathway.Cancer cell international · 2021Article
- Review
- RABL6A Promotes Pancreatic Neuroendocrine Tumor Angiogenesis and Progression In Vivo.Biomedicines · 2021Article
- RABL6A Regulates Schwann Cell Senescence in an RB1-Dependent Manner.International journal of molecular sciences · 2021Article
- Prognostic and therapeutic value of the Hippo pathway, RABL6A, and p53-MDM2 axes in sarcomas.Oncotarget · 2021Article
- Perphenazine exerts antitumor effects on HUT78 cells through Akt dephosphorylation by protein phosphatase 2A.Oncology letters · 2021Article
- Combination therapies for MPNSTs targeting RABL6A-RB1 signaling.Oncotarget · 2021Article
- Loss of hepatic aldolase B activates Akt and promotes hepatocellular carcinogenesis by destabilizing the Aldob/Akt/PP2A protein complex.PLoS biology · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
29 authors at 6 institutions in 3 countries.
Funding
Abstract
Hyperactivated AKT/mTOR signaling is a hallmark of pancreatic neuroendocrine tumors (PNETs). Drugs targeting this pathway are used clinically, but tumor resistance invariably develops. A better understanding of factors regulating AKT/mTOR signaling and PNET pathogenesis is needed to improve current therapies. We discovered that RABL6A, a new oncogenic driver of PNET proliferation, is required for AKT activity. Silencing RABL6A caused PNET cell-cycle arrest that coincided with selective loss of AKT-S473 (not T308) phosphorylation and AKT/mTOR inactivation. Restoration of AKT phosphorylation rescued the G1 phase block triggered by RABL6A silencing. Mechanistically, loss of AKT-S473 phosphorylation in RABL6A-depleted cells was the result of increased protein phosphatase 2A (PP2A) activity. Inhibition of PP2A restored phosphorylation of AKT-S473 in RABL6A-depleted cells, whereas PP2A reactivation using a specific small-molecule activator of PP2A (SMAP) abolished that phosphorylation. Moreover, SMAP treatment effectively killed PNET cells in a RABL6A-dependent manner and suppressed PNET growth in vivo. The present work identifies RABL6A as a new inhibitor of the PP2A tumor suppressor and an essential activator of AKT in PNET cells. Our findings offer what we believe is a novel strategy of PP2A reactivation for treatment of PNETs as well as other human cancers driven by RABL6A overexpression and PP2A inactivation.
Indexed as
Identifiers
What OpenQuestion holds
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.