ArticleOncogene2019
Signal peptide peptidase promotes tumor progression via facilitating FKBP8 degradation.
Article in Oncogene, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 44 citations in OpenAlex.
- Dimeric architecture and membrane thinning govern substrate recognition by human signal peptide peptidase.Research square · 2026Article
- MicroRNA-663a upregulation upon ARID1A depletion promotes the growth and migration of esophageal cancer cells by targeting FKBP8.Translational cancer research · 2026Article
- Elemene Augments the Effects of Anti-PD-1 Immunotherapy on Hepatocellular Carcinoma by Regulating the miR-130a-5p/SPP/MHC-I Axis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- CircSATB1 Promotes Colorectal Cancer Liver Metastasis through Facilitating FKBP8 Degradation via RNF25-Mediated Ubiquitination.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- The DNase TREX1 is a substrate of the intramembrane protease SPP with implications for disease pathogenesis.Cellular and molecular life sciences : CMLS · 2025Article
- Knockdown of HM13 Inhibits Metastasis, Proliferation, and M2 Macrophage Polarization of Non-small Cell Lung Cancer Cells by Suppressing the JAK2/STAT3 Signaling Pathway.Applied biochemistry and biotechnology · 2025Article
- Topology surveillance of the lanosterol demethylase CYP51A1 by signal peptide peptidase.Journal of cell science · 2024Article
- Selective regulation of aspartyl intramembrane protease activity by calnexin.Cellular and molecular life sciences : CMLS · 2024Article
- Review
- Proteomic analysis of the effect of hemin in breast cancer.Scientific reports · 2023Article
- Exploring the relationship between abnormally high expression ofFrontiers in oncology · 2023Article
- Histocompatibility Minor 13 (HM13), targeted by miR-760, exerts oncogenic role in breast cancer by suppressing autophagy and activating PI3K-AKT-mTOR pathway.Cell death & disease · 2022Article
- The role of cellular proteostasis in antitumor immunity.The Journal of biological chemistry · 2022Review
- Pan-cancer analysis suggests histocompatibility minor 13 is an unfavorable prognostic biomarker promoting cell proliferation, migration, and invasion in hepatocellular carcinoma.Frontiers in pharmacology · 2022Article
- Synergistic Interactions of Cannabidiol with Chemotherapeutic Drugs in MCF7 Cells: Mode of Interaction and Proteomics Analysis of Mechanisms.International journal of molecular sciences · 2021Article
- Prohibitin regulates mTOR pathway via interaction with FKBP8.Frontiers of medicine · 2021Article
- Knockdown of GTF2E2 inhibits the growth and progression of lung adenocarcinoma via RPS4X in vitro and in vivo.Cancer cell international · 2021Article
- FKBP10 promotes proliferation of glioma cells via activating AKT-CREB-PCNA axis.Journal of biomedical science · 2021Article
- Nuclear Localization of Heme Oxygenase-1 in Pathophysiological Conditions: Does It Explain the Dual Role in Cancer?Antioxidants (Basel, Switzerland) · 2021Review
- Mounting evidence of FKBP12 implication in neurodegeneration.Neural regeneration research · 2020Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Signal peptide peptidase (SPP) is an endoplasmic reticulum (ER)-resident aspartyl protease mediating intramembrane cleavage of type II transmembrane proteins. Increasing evidence has supported the role of SPP in ER-associated protein degradation. In the present study, we show that SPP expression is highly induced in human lung and breast cancers and correlated with disease outcome. Stable depletion of SPP expression in lung and breast cancer cell lines significantly reduced cell growth and migration/invasion abilities. Quantitative analysis of the proteomic changes of microsomal proteins in lung cancer cells by the stable isotope labeling with amino acids in cell culture (SILAC) approach revealed that the level of FKBP8, an endogenous inhibitor of mTOR, was significantly increased following SPP depletion. Co-immunoprecipitation assay and confocal immunofluorescence demonstrated that SPP interacted and colocalized with FKBP8 in ER, supporting that FKBP8 is a protein substrate of SPP. Cycloheximide chase and proteasome inhibition experiments revealed that SPP-mediated proteolysis facilitated FKBP8 protein degradation in cytosol. Further experiment demonstrated that the levels of phosphorylation in mTOR and its downstream effectors, S6K and 4E-BP1, were significantly lower in SPP-depleted cells. The reduced mTOR signaling and decreases of growth and migration/invasion abilities induced by SPP depletion in cancer cells could be reversed by FKBP8 downregulation. The implication of FKBP8 in SPP-mediated tumorigenicity was also observed in the xenograft model. Together, these findings disclose that SPP promotes tumor progression, at least in part, via facilitating the degradation of FKBP8 to enhance mTOR signaling.
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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.