ArticleCell death & disease2015
KLF17 empowers TGF-β/Smad signaling by targeting Smad3-dependent pathway to suppress tumor growth and metastasis during cancer progression.
Article in Cell death & disease, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 53 citations in OpenAlex.
- KLF family of proteins in gastrointestinal tumors (Review).Oncology letters · 2026Review
- KLF18 is a necessary component of the DUX4-initiated transcriptional network and a candidate locus for phenotypic diversity.Genes & development · 2026Article
- LncRNA CDIPTOSP-induced destabilization of KLF17 promotes ovarian cancer progression through STAU1-mediated mRNA decay.American journal of translational research · 2026Article
- Alterations of Krüppel-like Factor Signaling and Potential Targeted Therapy for Hepatocellular Carcinoma.Anti-cancer agents in medicinal chemistry · 2025Review
- Prognostic value of KLFs family genes in renal clear cell carcinoma.Scientific reports · 2024Article
- Abnormal expression of Krüppel-like transcription factors and their potential values in lung cancer.Heliyon · 2024Review
- Functional Enrichment Analysis of Tumor Microenvironment-Driven Molecular Alterations That Facilitate Epithelial-to-Mesenchymal Transition and Distant Metastasis.Bioinformatics and biology insights · 2024Article
- Natriuretic Peptide Signaling in Uterine Biology and Preeclampsia.International journal of molecular sciences · 2023Review
- Krüppel-like factors in tumors: Key regulators and therapeutic avenues.Frontiers in oncology · 2023Review
- The functions and roles of C2H2 zinc finger proteins in hepatocellular carcinoma.Frontiers in physiology · 2023Review
- KLF17 promotes human naive pluripotency through repressing MAPK3 and ZIC2.Science China. Life sciences · 2022Article
- Bioinformatics analysis of KLF2 as a potential prognostic factor in ccRCC and association with epithelial-mesenchymal transition.Experimental and therapeutic medicine · 2022Article
- Tumor Microenvironment of Hepatocellular Carcinoma: Challenges and Opportunities for New Treatment Options.International journal of molecular sciences · 2022Review
- Immunosuppressive Signaling Pathways as Targeted Cancer Therapies.Biomedicines · 2022Review
- Review
- Review
- KLF17 promotes human naïve pluripotency but is not required for its establishment.Development (Cambridge, England) · 2021Article
- Effect ofThe Journal of international medical research · 2021Article
- Non-Coding RNAs Set a New Phenotypic Frontier in Prostate Cancer Metastasis and Resistance.International journal of molecular sciences · 2021Review
- Krüppel-like factor 17 upregulates uterine corin expression and promotes spiral artery remodeling in pregnancy.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Inhibition of tumor suppressive signaling is linked to cancer progression, metastasis and epithelial-mesenchymal transition (EMT). Transforming growth factor-β1 (TGF-β)/Smad signaling plays an important role in tumor suppression. Kruppel-like-factor 17 (KLF17) is a negative regulator of metastasis and EMT. However, underlying mechanisms leading to tumor suppressive and anti-metastatic function of KLF17 still remains unknown. Here, we show that KLF17 plays an integral role in potentiating TGF-β/Smad signaling via Smad3-dependent pathway to suppress tumor progression. Intriguingly, TGF-β/Smad3 signaling induces KLF17 expression, generating a positive feedback loop. TGF-β/Smad3-KLF17 loop is critical for anti-metastasis and tumor inhibition in cancer cells. Mechanistically, silencing KLF17 reduced Smad3-DNA complex formation on Smad binding element (SBE) and affects the expression of TGF-β/Smad target genes. Moreover, KLF17 alters Smad3 binding pattern on chromatin. KLF17 regulates TGF-β target genes that are Smad3-dependent. Smad3 and KLF17 physically interact with each other via KLF17 responsive elements/SBE region. Intriguingly, TGF-β stimulates the recruitment of KLF17 on chromatin to subsets of metastasis-associated genes. Functionally, depletion of KLF17 enhanced tumorigenic features in cancer cells. KLF17 is critical for full cytostatic function of TGF-β/Smad signaling. Clinically, KLF17 expression significantly decreases during advance HCC. KLF17 shows positive correlation with Smad3 levels in cancer samples. Our data shows that enhance KLF17 activity has important therapeutic implications for targeted-therapies aimed at TGF-β/Smad3 pathway. These findings define novel mechanism by which TGF-β/Smad-KLF17 pathway mutually affect each other during cancer metastasis, provide a new model of regulation of TGF-β/Smad signaling by KLF17 and defines new insights into anti-metastatic function of KLF17.
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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.