mTOR-dependent transcriptional repression of Pdcd4 tumor suppressor in lung cancer cells
Abstract
Programmed cell death 4 (Pdcd4) tumor suppressor is frequently lost in tumors of various origins including lung cancer, and its loss contributes to tumor progression. However molecular mechanisms underlying Pdcd4 suppression in lung cancer cells remain largely unexplored. Here we investigated molecular mechanisms of Pdcd4 suppression in lung cancer cells. Besides enhanced mTOR-dependent proteasomal degradation of Pdcd4 protein, we found that Pdcd4 transcription is negatively regulated by mTOR signaling, and localized cis-acting element in Pdcd4 promoter responsible for this effect. In conclusion, we described a novel molecular mechanism of Pdcd4 suppression in cancer cells consisting from mTOR signaling-dependent transcriptional repression of Pdcd4.
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EGF contributes to downregulate PDCD4 expression at both levels of transcription and protein degradation and PDCD4 transcription is controlled by mTOR or its downstream signaling pathway.
“The results indicate that EGF contributes to downregulate PDCD4 expression at both levels of transcription and protein degradation and that PDCD4 transcription is controlled by mTOR or its downstream signaling pathway.”
From Control Mechanisms of the Tumor Suppressor PDCD4: Expression and Functions (2019) · cites this paper as [73]
Transcription of PDCD4 was repressed in an mTOR-signaling dependent manner in lung cancer cells.
“Vihreva et al. reported that the transcription of PDCD4 was repressed in mTOR-signaling dependent manner, in lung cancer cells [73].”
From Control Mechanisms of the Tumor Suppressor PDCD4: Expression and Functions (2019) · cites this paper as [73]
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References 57 · Cited by 13
- Authors
- Vikhreva, P. N., Shepelev, M. V., & Korobko, I. V.
- Affiliations
- Russian Academy of Sciences (RU)
- Corresponding author
- Korobko, I.V.
- Venue
- Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms
- Publisher
- Elsevier BV
- Published
- 2014-01
- Volume
- 1839
- Issue
- 1
- Pages
- 43-49
- ISSN
- 1874-9399 (ISSN-L)
- OpenAlex
- W2081669958
- Cited by
- 13
- References
- 57
- Citations by year
- 2026: 1 · 2025: 1 · 2020: 1 · 2019: 1 · 2018: 4 · 2017: 2 · 2015: 2 · 2014: 1
- FWCI
- 0.45
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mechanisms of cancer metastasis
- Keywords
- PDCD4, tumor suppressor, mTOR signaling, transcriptional repression, lung cancer, proteasomal degradation, gene expression regulation
- MeSH terms
- Cytoplasm, Humans, Lung Neoplasms, Transcription, Genetic, Signal Transduction, Gene Expression Regulation, Neoplastic, Genes, Tumor Suppressor, RNA-Binding Proteins, Cell Line, Tumor, Proteasome Endopeptidase Complex, Apoptosis Regulatory Proteins, TOR Serine-Threonine Kinases, Proteolysis
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