E-Cadherin, Integrin Alpha2 (Cd49b), and Transferrin Receptor-1 (Tfr1) Are Promising Immunohistochemical Markers of Selected Adverse Pathological Features in Patients Treated with Radical Prostatectomy

Zapała, Piotr; Fus, Łukasz; Lewandowski, Zbigniew; Garbas, Karolina; Zapała, Łukasz; Górnicka, Barbara; Radziszewski, Piotr

doi:10.3390/jcm10235587

Cited by 3 publications

(1 citation statement)

References 36 publications

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“…The iron contents in PCa cells are higher that the adjacent non-cancerous prostate tissues (Guntupalli et al , 2007; Sarafanov et al , 2011). TFR1 is the major receptor for cellular iron import, the expression of which is significantly elevated in PCa, which has the potential to serve as a marker of PCa diagnosis and prognosis (Keer et al , 1990; Zapała et al , 2021). In the present results, we found that FGFR1 increased expression of TFR1, depletion of FGFR1 downregulated TFR1 expression, is obviously decreased.…”

Section: Discussionmentioning

confidence: 99%

FGFR1 governs iron metabolism via regulating post-translational modification of IRP2 in prostate cancer cells

Lin

Wang

et al. 2022

Preprint

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The acquisition of ectopic fibroblast growth factor receptor 1 (FGFR1) expression is well documented in prostate cancer (PCa) progression. However, how FGFR1 facilitates PCa progression is not fully revealed, although it is known to confer tumor growth advantage and metastasis. Here we report that FGFR1 deletion in DU145 human PCa cells retards the iron metabolism and reduces transferrin receptor 1 (TFR1), which synergistically enhances the anti-cancer effect of iron chelator. FGFR1 and TFR1 are highly expressed in PCa, and FGFR1 overexpression increased TFR1 in PCa cell lines. Furthermore, we first time demonstrate that FGFR1 deletion boosts and shifts the degradation of iron regulatory proteins 2 (IRP2) to downregulate TFR1. Detailed characterization revealed that based on FGFR1 deletion the stability of IRP2 is broken, whose degradation is accelerated, which can be not observed without FGFR1 deletion. In addition, IRP2 overexpression rescue the malignancy degree of DU145 cells. Our results here unravel a novel mechanism by which FGFR1 promotes PCa progression by upregulating iron metabolism, and that the FGFR1/IRP2/TFR1 axis can be a potential target for managing PCa progression.

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Section: Discussionmentioning

confidence: 99%

FGFR1 governs iron metabolism via regulating post-translational modification of IRP2 in prostate cancer cells

Lin

Wang

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

FGFR1 governs iron homeostasis via regulating intracellular protein degradation pathways of IRP2 in prostate cancer cells

Lin,

Shi

et al. 2024

Commun Biol

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The acquisition of ectopic fibroblast growth factor receptor 1 (FGFR1) expression is well documented in prostate cancer (PCa) progression, notably in conferring tumor growth advantage and facilitating metastasis. However, how FGFR1 contributes to PCa progression is not fully revealed. Here we report that ectopic FGFR1 in PCa cells promotes transferrin receptor 1 (TFR1) expression and expands the labile iron pool (LIP), and vice versa. We further demonstrate that FGFR1 stabilizes iron regulatory proteins 2 (IRP2) and therefore, upregulates TFR1 via promoting IRP2 binding to the IRE of TFR1. Deletion of FGFR1 in DU145 cells decreases the LIP, which potentiates the anticancer efficacy of iron chelator. Intriguingly, forced expression of IRP2 in FGFR1 depleted cells reinstates TFR1 expression and LIP, subsequently restoring the tumorigenicity of the cells. Together, our results here unravel a new mechanism by which FGFR1 drives PCa progression and suggest a potential novel target for PCa therapy.

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FGFR1 governs iron metabolism via regulating post-translational modification of IRP2 in prostate cancer cells

Lin

Shi

Zhou

et al. 2022

Preprint

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Background The acquisition of ectopic fibroblast growth factor receptor 1 (FGFR1) expression is well documented in prostate cancer (PCa) progression. However, how FGFR1 facilitates PCa progression is not fully revealed, although it is known to confer tumor growth advantage and metastasis. Here we report that FGFR1 deletion in DU145 human PCa cells retards the iron metabolism and reduces transferrin receptor 1 (TFR1), which synergistically enhances the anti-cancer effect of iron chelator. Methods Prostate/PCa tissues from various ages of wildtype and TRAMP mice were collected to investigate FGFR1 expression and iron content for association with prostate cancer development and progression. FGFR1 null DU145 cells (DU145ΔR1 cells) were generated to analyze the association of FGFR1 expression with iron metabolism in PCa using iron assay kit, Western blot and qRT-PCR. Meanwhile, DFO, an iron-chelating agent, treated PCa cells to determine whether ablation of FGFR1 sensitized the cells to iron deficiency. Next, we assessed the association of TFR1 expression with Gleason scores in PCa patients through searching from the TCGA database, and investigated the relationship of FGFR1 with TFR1 expression under IRP2 regulation. Results FGFR1 and TFR1 are highly expressed in PCa, and FGFR1 overexpression increased TFR1 in PCa cell lines. Furthermore, we first time demonstrate that FGFR1 deletion boosts and shifts the degradation of iron regulatory proteins 2 (IRP2) to downregulate TFR1. Detailed characterization revealed that based on FGFR1 deletion the stability of IRP2 is broken, whose degradation is accelerated, which can be not observed without FGFR1 deletion. In addition, IRP2 overexpression rescue the malignancy degree of DU145 cells. Conclusion Our results here unravel a novel mechanism by which FGFR1 promotes PCa progression by upregulating iron metabolism, and that the FGFR1/IRP2/TFR1 axis can be a potential target for managing PCa progression.

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E-Cadherin, Integrin Alpha2 (Cd49b), and Transferrin Receptor-1 (Tfr1) Are Promising Immunohistochemical Markers of Selected Adverse Pathological Features in Patients Treated with Radical Prostatectomy

Cited by 3 publications

References 36 publications

FGFR1 governs iron metabolism via regulating post-translational modification of IRP2 in prostate cancer cells

FGFR1 governs iron metabolism via regulating post-translational modification of IRP2 in prostate cancer cells

FGFR1 governs iron homeostasis via regulating intracellular protein degradation pathways of IRP2 in prostate cancer cells

FGFR1 governs iron metabolism via regulating post-translational modification of IRP2 in prostate cancer cells

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