Related Experiment Video
Updated: Jan 19, 2026
Generation of Prostate Cancer Cell Models of Resistance to the Anti-mitotic Agent Docetaxel
Published on: September 8, 2017
KLF5 downregulation desensitizes castration-resistant prostate cancer cells to docetaxel by increasing BECN1
Jing Jia1,2, Hai-Bao Zhang1, Qi Shi1
1Department of Urology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China, 710061.
Abstract:
KLF5 is frequently deleted or downregulated in prostate cancer. However, it is not known whether downregulation of KLF5 is associated with the response of prostate cancer cells to chemotherapy and/or prognosis of patients. Methods: We monitored cell growth by MTT and colony formation assays, and cell autophagy through tandem fluorescence microscopy and transmission electron microscopy. Gene expression was analyzed by RT-qPCR and Western blotting. We determined the binding of KLF5 together with HDAC3 on the beclin-1 (BECN1) promoter by the ChIP assay, oligonucleotides pulldown, and co-immunoprecipitation. The effect of docetaxel on cell growth in vivo was examined in a CWR22RV1 xenograft tumor mouse model. Results: In the present study, we found that KLF5 down-regulation was associated with progression of prostate cancer and poor prognosis of patients. KLF5 knockdown reduced the sensitivity of prostate cancer cells to docetaxel in vitro and in vivo, and docetaxel treatment decreased the expression of KLF5. Moreover, we confirmed that docetaxel treatment inhibited cell death by inducing autophagy in prostate cancer cells. Thus, we hypothesized that KLF5 could be a regulator of cell autophagy. Interestingly, KLF5 could inhibit prostate cancer cell autophagy by suppressing the transcription of BECN1 cooperatively with HDAC3. Another significant finding was that docetaxel treatment repressed KLF5 expression through AMPK/mTOR/p70S6K signaling pathway resulting in increased BECN1, induction of cell autophagy, and promotion of cell survival in castration-resistant prostate cancer cells. Conclusions: Our results indicated that downregulation of KLF5 promoted cell autophagy in prostate cancer. Furthermore, reduced KLF5 also facilitated cell autophagy induced by docetaxel resulting in desensitization to the drug and cell survival. Decreased levels of KLF5 led to increased BECN1 via AMPK/mTOR/p70S6K signaling. Thus, repression of BECN1 and cell autophagy was critical for KLF5 to increase the sensitivity of prostate cancer cells to docetaxel.
Insights
Downregulation of KLF5 in prostate cancer promotes autophagy and reduces docetaxel sensitivity. KLF5 normally suppresses autophagy by inhibiting BECN1 transcription, enhancing chemotherapy response.
Area of Science:
- Oncology
- Molecular Biology
- Cellular Biology
Background:
- Krüppel-like factor 5 (KLF5) is often downregulated in prostate cancer, but its role in chemotherapy response and patient prognosis is unclear.
- Understanding KLF5's function is crucial for developing effective prostate cancer treatments.
Purpose of the Study:
- To investigate the association between KLF5 downregulation and prostate cancer progression, patient prognosis, and response to docetaxel chemotherapy.
- To elucidate the molecular mechanisms by which KLF5 regulates autophagy and influences docetaxel sensitivity.
Main Methods:
- Cell growth assays (MTT, colony formation), autophagy monitoring (fluorescence microscopy, electron microscopy).
- Gene expression analysis (RT-qPCR, Western blotting), ChIP assays, co-immunoprecipitation.
- In vivo studies using a prostate cancer xenograft mouse model.
Main Results:
- KLF5 downregulation correlates with prostate cancer progression and poor prognosis.
- KLF5 knockdown decreases sensitivity to docetaxel in vitro and in vivo; docetaxel reduces KLF5 expression.
- KLF5 inhibits autophagy by suppressing BECN1 transcription via HDAC3; docetaxel induces autophagy by repressing KLF5 through AMPK/mTOR/p70S6K signaling.
Conclusions:
- KLF5 downregulation promotes prostate cancer cell autophagy and docetaxel resistance.
- Reduced KLF5 enhances docetaxel-induced autophagy, leading to drug desensitization and cell survival.
- KLF5's repression of BECN1 and autophagy is critical for enhancing docetaxel sensitivity in prostate cancer.
Related Concept Videos
01:15Receptor Downregulation in MVBs
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...
01:12GPCR Desensitization