Ectopic NGAL expression can alter sensitivity of breast cancer cells to EGFR, Bcl-2, CaM-K inhibitors and the plant natural product berberine

Chappell, William H.; Abrams, Stephen L.; Franklin, Richard A.; LaHair, Michelle M.; Montalto, Giuseppe; Cervello, Melchiorre; Martelli, Alberto M.; Nicoletti, Ferdinando; Candido, Saverio; Libra, Massimo; Polesel, Jerry; Talamini, Renato; Milella, Michèle; Tafuri, Agostino; Steelman, Linda S.; McCubrey, James A.

doi:10.4161/cc.22786

Cited by 23 publications

(21 citation statements)

References 197 publications

(231 reference statements)

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“…Our recent studies indicate that increased NGAL expression did not alter the sensitivity of the MCF-7 breast cancer cell line to the chemotherapeutic drug doxorubicin [36]. However, ectopic NGAL expression did alter the sensitivity of breast cancer cells to targeted therapy [37]. Furthermore, NGAL was found to be a predictive marker for complete response after neo-adjiuvant chemotherapy in low-risk subgroups of breast cancer patients and may be considered as an independent prognostic factor for decreased disease free survival in primary human breast cancer [38].…”

Section: Discussionmentioning

confidence: 99%

Roles of neutrophil gelatinase-associated lipocalin (NGAL) in human cancer

Candido

Maestro²,

Polesel³

et al. 2014

Oncotarget

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115

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Cancer remains one of the major cause of death in the Western world. Although, it has been demonstrated that new therapies can improve the outcome of cancer patients, still many patients relapse after treatment. Therefore, there is a need to identify novel factors involved in cancer development and/or progression. Recently, neutrophil gelatinase-associated lipocalin (NGAL) has been suggested as a key player in different cancer types. Its oncogenic effect may be related to the complex NGAL/MMP-9. In the present study, NGAL was analyzed at both transcript and protein levels in different cancer types by analysing 38 public available microarray datasets and the Human Protein Atlas tool.NGAL transcripts were significantly higher in the majority of solid tumors compared to the relative normal tissues for every dataset analyzed. Furthermore, concordance of NGAL at both mRNA and protein levels was observed for 6 cancer types including bladder, colorectal, liver, lung, ovarian, and pancreatic. All metastatic tumors showed a decrease of NGAL expression when compared to matched primary lesions.According to these results, NGAL is a candidate marker for tumor growth in a fraction of solid tumors. Further investigations are required to elucidate the function of NGAL in tumor development and metastatic processes.

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Section: Discussionmentioning

confidence: 99%

Roles of neutrophil gelatinase-associated lipocalin (NGAL) in human cancer

Candido

Maestro²,

Polesel³

et al. 2014

Oncotarget

Self Cite

115

View full text Add to dashboard Cite

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“…Also the effects of combinations of doxorubicin in the presence and absence of small molecule inhibitors were determined to ascertain whether the small molecule inhibitors could lower the concentrations of doxorubicin required to reach the IC 50 for doxorubicin [118]. NGAL expression was abundantly detected in all the cells infected with a retrovirus encoding NGAL [118].…”

Section: Effects Of Ectopic Ngal Expression On Sensitivity To Small Mmentioning

confidence: 99%

“…The effects of ectopic NGAL expression (induced by introduction of a retrovirus encoding the wild type NGAL gene) on the sensitivity of breast epithelial (MCF-10A), breast cancer (MCF-7), and CRC (HT-29) cells to small molecule inhibitors were examined [118]. Also the effects of combinations of doxorubicin in the presence and absence of small molecule inhibitors were determined to ascertain whether the small molecule inhibitors could lower the concentrations of doxorubicin required to reach the IC 50 for doxorubicin [118].…”

Section: Effects Of Ectopic Ngal Expression On Sensitivity To Small Mmentioning

confidence: 99%

Roles of NGAL and MMP-9 in the tumor microenvironment and sensitivity to targeted therapy

Candido

Abrams

Steelman

et al. 2016

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

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Various, diverse molecules contribute to the tumor microenvironment and influence invasion and metastasis. In this review, the roles of neutrophil gelatinase-associated lipocalin (NGAL) and matrix metalloproteinase-9 (MMP-9) in the tumor microenvironment and sensitivity to therapy will be discussed. The lipocalin family of proteins has many important functions. For example when NGAL forms a complex with MMP-9 it increases its stability which is important in cancer metastasis. Small hydrophobic molecules are bound by NGAL which can alter their entry into and efflux from cells. Iron transport and storage are also influenced by NGAL activity. Regulation of iron levels is important for survival in the tumor microenvironment as well as metastasis. Innate immunity is also regulated by NGAL as it can have bacteriostatic properties. NGAL and MMP-9 expression may also affect the sensitivity of cancer cells to chemotherapy as well as targeted therapy. Thus NGAL and MMP-9 play important roles in key processes involved in metastasis as well as response to therapy. This article is part of a Special Issue entitled: Tumor Microenvironment Regulation of Cancer Cell Survival, Metastasis, Inflammation, and Immune Surveillance edited by Peter Ruvolo and Gregg L. Semenza.

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“…Under physiological conditions, Bcl-2 is engaged in the movement, migration, adhesion and mitosis of cells, and is associated with cell senescence and apoptosis. Bcl-2 simulates FAS passage to launch cell apoptosis by linking the actin cytoskeleton and FAS protein [14,15]. When the FAS-Bcl-2 link is abnormal, it will influence the reactivity of the FAS-induced cell apoptosis to induce anti-apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Expressions of FHIT, BCRP and Bcl-2 Proteins in Breast Invasive Ductal Carcinoma

Li¹

2019

SJPH

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Objective: To explore the expressions of FHIT (Human fragile histidine triad), BCRP (breast cancer resistance protein) and Bcl-2 proteins in breast invasive ductal carcinoma (IDC) and its relationship with clinical pathological factors. Methods: The expressions of FHIT, BCRP and Bcl-2 proteins in 84 cases of intraoperative resection of primary breast IDC and 36 cases of normal breast tissue about 3 cm away from the neoplastci foci were detected with the method of immunohistochemical streptavidin-peroxidase (SP) to analyze the relationship between the three proteins and the pathological features of breast IDC. Results: The positive expression rates of FHIT, of BCRP and Bcl-2 were 42.86%, 72.62% and 61.90% respectively in the breast IDC group and 72.22%, 36.11% and 38.89 % respectively in the normal breast tissue control group, between which the differences were statistically significant (P <0.05). In the IDC group, the expression of the three proteins was related to the lymph nodes metastasis and tumor recurrence of breast IDC, but was not significantly correlated with the expression of estrogen receptor (ER), progesterone receptor (PR) and proto-oncogene human epidermal growth factor receptor 2 (Her-2). The expression of FHIT was negatively correlated with the expression of and Bcl-2 (r = -0.322, -0.389), but BCRP and Bcl-2 expression were positively correlated (r = 0.276). Conclusion: The abnormal expressions of FHIT, BCRP and Bcl-2 proteins in breast IDC may play an important role in its onset and development.

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Ectopic NGAL expression can alter sensitivity of breast cancer cells to EGFR, Bcl-2, CaM-K inhibitors and the plant natural product berberine

Cited by 23 publications

References 197 publications

Roles of neutrophil gelatinase-associated lipocalin (NGAL) in human cancer

Roles of neutrophil gelatinase-associated lipocalin (NGAL) in human cancer

Roles of NGAL and MMP-9 in the tumor microenvironment and sensitivity to targeted therapy

Expressions of FHIT, BCRP and Bcl-2 Proteins in Breast Invasive Ductal Carcinoma

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