Expression of cutaneous fatty acid-binding protein (C-FABP) in prostate cancer: Potential prognostic marker and target for tumourigenicity-suppression

Morgan, Elwin A; Forootan, Shiva S.; Adamson, Janet; Foster, Christopher S.; Fujii, Hiroshi; Igarashi, Michihiro; Beesley, Carol; Smith, Paul; Ke, Youqiang

doi:10.3892/ijo.32.4.767

Cited by 21 publications

(2 citation statements)

References 26 publications

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“…So the ability of RA to favor apoptosis rather than cellular survival, or conversely, is closely related to the expression levels of the two RA binding proteins, since CRABPII shuttles RA towards RAR and FABP5 versus PPARβ/δ [30]. Accordingly, it has been reported that the malignant progression in human cancers is associated with malignant progression [125]. Consequently, in some tumors, the expression of PPARβ/δ target genes is favored rather than RAR, thus favoring tumor growth [126].…”

Section: Ra/rar Signaling Involvement In Apoptosismentioning

confidence: 99%

The Pleiotropic Role of Retinoic Acid/Retinoic Acid Receptors Signaling: From Vitamin A Metabolism to Gene Rearrangements in Acute Promyelocytic Leukemia

Conserva

Anelli

Zagaria

et al. 2019

IJMS

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The family of retinoic acid receptors (RARs: RARα, -β, and -γ) has remarkable pleiotropy characteristics, since the retinoic acid/RARs pathway is involved in numerous biological processes not only during embryonic development, but also in the postnatal phase and during adulthood. In this review, we trace the roles of RA/RARs signaling in the immune system (where this pathway has both an immunosuppressive role or is involved in the inflammatory response), in hematopoiesis (enhancing hematopoietic stem cell self-renewal, progenitor cells differentiation or maintaining the bone marrow microenvironment homeostasis), and in bone remodeling (where this pathway seems to have controversial effects on bone formation or osteoclast activation). Moreover, in this review is shown the involvement of RAR genes in multiple chromosomal rearrangements generating different fusion genes in hematological neoplasms, with a particular focus on acute promyelocytic leukemia and its variant subtypes. The effect of different RARs fusion proteins on leukemic transformation, on patients’ outcome, and on therapy response is also discussed.

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Section: Ra/rar Signaling Involvement In Apoptosismentioning

confidence: 99%

The Pleiotropic Role of Retinoic Acid/Retinoic Acid Receptors Signaling: From Vitamin A Metabolism to Gene Rearrangements in Acute Promyelocytic Leukemia

Conserva

Anelli

Zagaria

et al. 2019

IJMS

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“…One of the genes involved in promoting malignant progression of prostate cancer cells is fatty acid‐binding protein 5 ( FABP5 ) (McKillop et al, 2019; Morgan et al, 2008). FABP5 is a member of the fatty acid‐binding protein (FABP) family and is a 15 kDa cytosolic protein that binds, with a high affinity, to long and middle chain fatty acids (Cucchi et al, 2019; Liu & Godbout, 2020; Madsen et al, 1992).…”

Section: Introductionmentioning

confidence: 99%

Molecular mechanisms on how FABP5 inhibitors promote apoptosis‐induction sensitivity of prostate cancer cells

Zhang

Jin

et al. 2023

Cell Biology International

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Previous work showed that FABP5 inhibitors suppressed the malignant progression of prostate cancer cells, and this suppression might be achieved partially by promoting apoptosis. But the mechanisms involved were not known. Here, we investigated the effect of inhibitors on apoptosis and studied the relevant mechanisms. WtrFABP5 significantly reduced apoptotic cells in 22Rv1 and PC3 by 18% and 42%, respectively. In contrast, the chemical inhibitor SB‐FI‐26 produced significant increases in percentages of apoptotic cells in 22Rv1 and PC3 by 18.8% (±4.1) and 4.6% (±1.1), respectively. The bio‐ inhibitor dmrFABP5 also did so by 23.1% (±2.4) and 15.8% (±3.0), respectively, in these cell lines. Both FABP5 inhibitors significantly reduced the levels of the phosphorylated nuclear fatty acid receptor PPARγ, indicating that these inhibitors promoted apoptosis‐induction sensitivity of the cancer cells by suppressing the biological activity of PPARγ. Thus, the phosphorylated PPARγ levels were reduced by FABP5 inhibitors, the levels of the phosphorylated AKT and activated nuclear factor kapper B (NFκB) were coordinately altered by additions of the inhibitors. These changes eventually led to the increased levels of cleaved caspase‐9 and cleaved caspase‐3; and thus, increase in the percentage of cells undergoing apoptosis. In untreated prostate cancer cells, increased FABP5 suppressed the apoptosis by increasing the biological activity of PPARγ, which, in turn, led to a reduced apoptosis by interfering with the AKT or NFκB signaling pathway. Our results suggested that the FABP5 inhibitors enhanced the apoptosis‐induction of prostate cancer cells by reversing the biological effect of FABP5 and its related pathway.

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Docetaxel/cabazitaxel and fatty acid binding protein 5 inhibitors produce synergistic inhibition of prostate cancer growth

et al. 2019

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Background Prostate cancer (PCa) remains the second leading cause of cancer‐related death among men. Taxanes, such as docetaxel and cabazitaxel are utilized in standard treatment regimens for chemotherapy naïve castration‐resistant PCa. However, tumors often develop resistance to taxane chemotherapeutics, highlighting a need to identify additional therapeutic targets. Fatty acid‐binding protein 5 (FABP5) is an intracellular lipid carrier whose expression is upregulated in metastatic PCa and increases cell growth, invasion, and tumor formation. Here, we assessed whether FABP5 inhibitors synergize with semi‐synthetic taxanes to induce cytotoxicity in vitro and attenuate tumor growth in vivo. Methods PC3, DU‐145, and 22Rv1 PCa cells were incubated with FABP5 inhibitors Stony Brook fatty acid‐binding protein inhibitor 102 (SBFI‐102) or SBFI‐103 in the presence or absence of docetaxel or cabazitaxel, and cytotoxicity was evaluated using the 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5 diphenyl tetrazolium bromide assay. Cytotoxicity of SBFI‐102 and SBFI‐103 was also evaluated in noncancerous cells. For the in vivo studies, PC3 cells were subcutaneously implanted into BALB/c nude mice, which were subsequently treated with FABP5 inhibitors, docetaxel, or a combination of both. Results SBFI‐102 and SBFI‐103 produced cytotoxicity in the PCa cells. Coincubation of the PCa cells with FABP5 inhibitors and docetaxel or cabazitaxel produced synergistic cytotoxic effects in vitro. Treatment of mice with FABP5 inhibitors reduced tumor growth and a combination of FABP5 inhibitors with a submaximal dose of docetaxel reduced tumor growth to a larger extent than treatment with each drug alone. Conclusions FABP5 inhibitors increase the cytotoxic and tumor‐suppressive effects of taxanes in PCa cells. The ability of these drugs to synergize could permit more efficacious antitumor activity while allowing for dosages of docetaxel or cabazitaxel to be lowered, potentially decreasing taxane‐resistance.

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Expression of cutaneous fatty acid-binding protein (C-FABP) in prostate cancer: Potential prognostic marker and target for tumourigenicity-suppression

Cited by 21 publications

References 26 publications

The Pleiotropic Role of Retinoic Acid/Retinoic Acid Receptors Signaling: From Vitamin A Metabolism to Gene Rearrangements in Acute Promyelocytic Leukemia

The Pleiotropic Role of Retinoic Acid/Retinoic Acid Receptors Signaling: From Vitamin A Metabolism to Gene Rearrangements in Acute Promyelocytic Leukemia

Molecular mechanisms on how FABP5 inhibitors promote apoptosis‐induction sensitivity of prostate cancer cells

Docetaxel/cabazitaxel and fatty acid binding protein 5 inhibitors produce synergistic inhibition of prostate cancer growth

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