FKBP4 regulates 5-fluorouracil sensitivity in colon cancer by controlling mitochondrial respiration

Zhu, Zhenyu; Hou, Qing; Wang, Bishi; Li, Changhao; Liu, Luguang; Gong, Weipeng; Chai, Jie; Guo, Hongbo; Jia, Yanhan

doi:10.26508/lsa.202201413

Cited by 7 publications

(5 citation statements)

References 62 publications

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“…Previous studies have shown that FKBP52 contributes to cancer cell proliferation and that FKBP52 expression is up-regulated in several cancers. These results indicate that high FKBP52 expression is linked with poor prognosis ( Ward et al, 1999 ; Lin et al, 2007 ; Liu et al, 2010 ; Mange et al, 2019 ; Meng et al, 2020 ; Liu & Gao, 2021 ; Zong et al, 2021 ; Habara et al, 2022 ; Maeda et al, 2022 ; Zhu et al, 2022 ). The mechanisms by which FKBP52 promotes cell proliferation in cancer cells include stabilization of ERα ( Habara et al, 2022 ), dimerization of ARs ( Maeda et al, 2022 ), and promotion of nuclear translocation of RelA ( Erlejman et al, 2014 ) and IKK complex formation ( Zong et al, 2021 ).…”

Section: Introductionmentioning

confidence: 80%

NFAT activation by FKBP52 promotes cancer cell proliferation by suppressing p53

Hanaki,

Habara,

Tomiyasu

et al. 2024

Life Sci. Alliance

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FK506-binding protein 52 (FKBP52) is a member of the FKBP family of proline isomerases. FKBP52 is up-regulated in various cancers and functions as a positive regulator of steroid hormone receptors. Depletion of FKBP52 is known to inhibit cell proliferation; however, the detailed mechanism remains poorly understood. In this study, we found that FKBP52 depletion decreasedMDM2transcription, leading to stabilization of p53, and suppressed cell proliferation. We identified NFATc1 and NFATc3 as transcription factors that regulateMDM2. We also found that FKBP52 associated with NFATc3 and facilitated its nuclear translocation. In addition, calcineurin, a well-known Ca2+phosphatase essential for activation of NFAT, plays a role inMDM2transcription. Supporting this notion,MDM2expression was found to be regulated by intracellular Ca2+. Taken together, these findings reveal a new role of FKBP52 in promoting cell proliferation via the NFAT-MDM2-p53 axis, and indicate that inhibition of FKBP52 could be a new therapeutic tool to activate p53 and inhibit cell proliferation.

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Section: Introductionmentioning

confidence: 80%

NFAT activation by FKBP52 promotes cancer cell proliferation by suppressing p53

Hanaki,

Habara,

Tomiyasu

et al. 2024

Life Sci. Alliance

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“…The rst proteins of the immunosuppressive drug cyclosporin, that were found were cyclophilins and FK506 binding proteins (FKBPs) 38 . According to recent studies, immunophilins are crucial for the intrinsic characteristics of a tumor [39][40][41] . The FKBP5 gene was the only immunophilin family member to be found to have a splicing variation 42 .…”

Section: Discussionmentioning

confidence: 99%

Circular RNA circDDX17 suppression to gastric cancer progression via the sponging miR-1208/miR-1279/FKBP5 axis and encodes a novel circDDX17-63aa protein

Liu,

Ma,

Xue

et al. 2023

Preprint

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Circular RNAs (circRNAs) have an important role in the development and progression of gastric cancer (GC). Hsa_circ_0063331 (circDDX17), a new circRNA shown to be considerably down-regulated in GC, was chosen for further study. The location of circDDX17 in GC cells was investigated using nuclear and cytoplasmic RNA fractionation and an RNA-FISH experiment. qRT-PCR was used to determine the expression levels of circDDX17, miR-1208, miR-1279, and FKBP5 in GC tissues. To investigate the functional mechanism of circDDX17 on the miR-1208/miR-1279/FKBP5 axis in GC cells, bioinformatics analysis, luciferase reporter, and IP were used. To investigate the role of circDDX17 and circDDX17-63aa in GC development, researchers used Transwell, wound healing, colony formation assays, CCK8, cell apoptosis tests, and Western blot. Finally, circDDX17 function in vivo was investigated using xenograft and metastatic mice models. We discovered that circDDX17 was down-regulated in GC tissues and cell lines in our investigation. CircDDX17 expression in GC patients was linked to tumor growth and lymph node metastasis. CircDDX17 decreased GC cell proliferation, migration, and epithelial-mesenchymal transition (EMT), while also promoting apoptosis in vitro and in vivo. CircDDX17 behaved as a sponge for miR-1208 and miR-1279, regulating FKBP5 expression in GC cells. FKBP5 interacts with ERK1/2 to control GC development through the ERK1/2 pathway. Furthermore, circDDX17 also encoded circDDX17-63aa, which inhibited GC cell proliferation, migration, and EMT. Finally, circDDX17 inhibits GC advancement via miR-1208/miR-1279/FKBP5 and encoded circDDX17-63aa to inhibit GC progression.

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“… 83 , 84 Although the knockdown of FKBP52 did not affect the growth of colon adenocarcinoma cell lines, increased sensitivity to 5‐fluorouracil was observed in FKBP52‐KD cells. 83 Additionally, FKBP4 was transcriptionally activated by E2F1. 84 The expression of FKBP52 is also increased in lung adenocarcinoma and is a poor prognostic factor for the disease.…”

Section: Expression Level Of Fkbp52 In Cancer Tiss...mentioning

confidence: 98%

“…Database analysis revealed that FKBP52 expression is increased in colorectal cancer 83,84 . Although the knockdown of FKBP52 did not affect the growth of colon adenocarcinoma cell lines, increased sensitivity to 5‐fluorouracil was observed in FKBP52‐KD cells 83 . Additionally, FKBP4 was transcriptionally activated by E2F1 84 .…”

Section: Expression Level Of Fkbp52 In Cancer Tissues and Its Relatio...mentioning

confidence: 99%

“…Prostate cancer Upregulated 37,68 Inhibition of proliferation 38 Upregulates AR dimerization 38 Breast cancer (ERα + ) Upregulated 46,77 Inhibition of proliferation 46 Upregulates ERα stability 46 Breast cancer (ERα − ) Upregulated 77,80 Inhibition of proliferation 80 Upregulates PI3K/AKT pathway 80 Colon cancer Upregulated 83,84 No effect 83 Resistance to 5-FU 83 Lung cancer Upregulated 56,85 Inhibition of proliferation 56,85 Upregulates PI3K/AKT pathway 85 Upregulates IKK/NF-κB pathway 56 Liver cancer Upregulated 86 No data No data…”

Section: Cancer Type Fkbp52 Expression Kd Role Of Fkbp52mentioning

confidence: 99%

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Impact of FKBP52 on cell proliferation and hormone‐dependent cancers

Hanaki

Shimada

2023

Cancer Science

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The FKBP family is a group of genes with an FK506 binding domain (FK domain, also known as the PPIase domain); 18 different genes have been identified in this family. 1 The domains of 16 genes are shown in Figure 1A, excluding FKBPL and FKBP1C. 2 Recent studies have reported that FKBP1C is a long noncoding RNA. 3 The FKBP family is characterized by the presence of pairs of genes with similar structures (e.g., FKBP12 and FKBP12.6). FKBP12 was the first gene discovered in the FKBP family, 4 and the other FKBPs were discovered based on their similarities with FKBP12. FKBP12 is the primary target of two well-known drugs, FK506 and rapamycin; when FKBP12 binds to FK506 or rapamycin, it inhibits calcineurin and rapamycin complex 1 (TORC1), respectively. High-molecular-weight FKBPs (large FKBPs) have a more complex structure than FKBP12, and some have multiple PPIase domains; FKBP51 and FKBP52 have

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FKBP4 regulates 5-fluorouracil sensitivity in colon cancer by controlling mitochondrial respiration

Cited by 7 publications

References 62 publications

NFAT activation by FKBP52 promotes cancer cell proliferation by suppressing p53

NFAT activation by FKBP52 promotes cancer cell proliferation by suppressing p53

Circular RNA circDDX17 suppression to gastric cancer progression via the sponging miR-1208/miR-1279/FKBP5 axis and encodes a novel circDDX17-63aa protein

Impact of FKBP52 on cell proliferation and hormone‐dependent cancers

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