Cellular levels of aldehyde dehydrogenases (ALDH1A1 and ALDH3A1) as predictors of therapeutic responses to cyclophosphamide-based chemotherapy of breast cancer: a retrospective study

Sládek, Norman E.; Kollander, Rahn; Sreerama, Lakshmaiah; Kiang, David T.

doi:10.1007/s00280-001-0412-4

Cited by 191 publications

(160 citation statements)

References 23 publications

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“…Apoptotic resistance is crucial for distant metastasis as breast cancer cells must survive for extended periods of time in the circulatory system to reach distant organs, such as the lung, a condition in which they are exposed to high risk of anoikis (56). A particularly interesting gene in the SND1-regulated lung metastasis enrichment core is ALDH3A1, which has been shown to promote resistance to various chemotherapeutic agents and other cell death-inducing toxins (57)(58)(59). Importantly, ALDH3A1 was also shown previously to promote MTDH-mediated resistance to chemotherapy-induced apoptosis (6).…”

Section: Discussionmentioning

confidence: 99%

Identification of Staphylococcal Nuclease Domain-containing 1 (SND1) as a Metadherin-interacting Protein with Metastasis-promoting Functions

Blanco

Alečković

Hua

et al. 2011

Journal of Biological Chemistry

114

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Metastasis is the deadliest and most poorly understood feature of malignant diseases. Recent work has shown that Metadherin (MTDH) is overexpressed in over 40% of breast cancer patients and promotes metastasis and chemoresistance in experimental models of breast cancer progression. Here we applied mass spectrometry-based screen to identify staphylococcal nuclease domain-containing 1 (SND1) as a candidate MTDH-interacting protein. After confirming the interaction between SND1 and MTDH, we tested the role of SND1 in breast cancer and found that it strongly promotes lung metastasis. SND1 was further shown to promote resistance to apoptosis and to regulate the expression of genes associated with metastasis and chemoresistance. Analyses of breast cancer clinical microarray data indicated that high expression of SND1 in primary tumors is strongly associated with reduced metastasis-free survival in multiple large scale data sets. Thus, we have uncovered SND1 as a novel MTDH-interacting protein and shown that it is a functionally and clinically significant mediator of metastasis.Metastasis is responsible for the majority of cancer-related deaths (1). An increasing number of genes have been implicated in mediating different steps of metastasis, but relatively few are mechanistically well characterized (2). One recently verified mediator of distant metastasis is Metadherin (MTDH 3 ; also called Lyric and AEG1 (3-5)). MTDH has been shown to be a key functional target of the 8q22 genomic gain that is frequently observed in poor prognosis breast cancer patients (6). Beyond promoting experimental lung metastasis (3, 6), multiple studies have implicated MTDH as a mediator of several cancer-related processes, such as oncogenesis and angiogenesis (7,8), invasion (9), chemoresistance (6, 10 -12), apoptosis resistance (13), and autophagy (14). Despite the abundance of MTDH phenotypes, a consensus understanding of its underlying molecular mechanisms has not yet been reached. MTDH has been shown to influence several oncogenic signaling pathways and transcription factors, such as Ha-Ras (15), PI3K/AKT (13), ERK, Wnt/␤-catenin (8), NF-B (16), c-Myc (15), and FOXO1/FOXO3a (17, 18). However, MTDH regulation of signaling pathways appears to be context-dependent with affected pathways varying by tumor type and cell line (19,20). Furthermore, prior work on MTDH molecular mechanisms has largely focused on hypothesis-driven investigations into the ability of MTDH to influence classical oncogenic pathways with little exploration to date on protein-level interactions (16,21).In this study, we aimed to expand the knowledge of MTDH molecular functionality and also uncover novel genes involved in promoting distant metastasis. Our approach utilized an unbiased, mass spectrometry-based screen for MTDH-interacting partners. We identified and characterized the interaction between MTDH and one such protein, SND1. SND1 is a multifunctional protein with reported roles in transcriptional activation (22), RNA editing (23, 24), formation of the RNAinduced ...

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Section: Discussionmentioning

confidence: 99%

Identification of Staphylococcal Nuclease Domain-containing 1 (SND1) as a Metadherin-interacting Protein with Metastasis-promoting Functions

Blanco

Alečković

Hua

et al. 2011

Journal of Biological Chemistry

114

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“…Seven of the eight validated genes overexpressed in current smokers-CYP1B1, four AKRs, ALDH3A1, and NQO1 (Table 2)-are involved in drug and/or carcinogen metabolism (9,10,(18)(19)(20)(21)(22)(23)(24)(25)(26)(27). Polycyclic aromatic hydrocarbons in tobacco smoke are known to bind to and activate the aryl hydrocarbon receptor and thus induce CYP1B1 (10).…”

Section: Discussionmentioning

confidence: 99%

Impact of Smoking Cessation on Global Gene Expression in the Bronchial Epithelium of Chronic Smokers

Zhang

Lee

Tang

et al. 2008

Cancer Prevention Research

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Cigarette smoke is the major cause of lung cancer and can interact in complex ways with drugs for lung cancer prevention or therapy. Molecular genetic research promises to elucidate the biological mechanisms underlying divergent drug effects in smokers versus nonsmokers and to help in developing new approaches for controlling lung cancer. The present study compared global gene expression profiles (determined via Affymetrix microarray measurements in bronchial epithelial cells) between chronic smokers, former smokers, and never smokers. Smoking effects on global gene expression were determined from a combined analysis of three independent data sets. Differential expression between current and never smokers occurred in 591 of 13,902 measured genes (P < 0.01 and >2-fold change; pooled data)-a profound effect. In contrast, differential expression between current and former smokers occurred in only 145 of the measured genes (P < 0.01 and >2-fold change; pooled data). Nine of these 145 genes showed consistent and significant changes in each of the three data sets (P < 0.01 and >2-fold change), with eight being down-regulated in former smokers. Seven of the eight down-regulated genes, including CYP1B1 and three AKR genes, influence the metabolism of carcinogens and/or therapeutic/chemopreventive agents. Our data comparing former and current smokers allowed us to pinpoint the genes involved in smoking-drug interactions in lung cancer prevention and therapy. These findings have important implications for developing new targeted and dosing approaches for prevention and therapy in the lung and other sites, highlighting the importance of monitoring smoking status in patients receiving oncologic drug interventions.

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“…Furthermore, Storms et al demonstrated that primitive hemtopoietic progenitors could be purified with ALDH activity suggesting, that ALDH1 might be a reliable marker for the isolation of stem cells (17). Increased ALDH1 activity has also been found in stem cell populations in acute myeloid leukemia and breast cancers, as well as their normal counterparts; mammary and hematopoietic stem cells, and has been found to be correlated with drug resistance and poor prognosis of patients (18)(19)(20). Thus, ALDH1 has been proposed as a common marker for both normal and malignant stem cells.…”

Section: Introductionmentioning

confidence: 95%

Possible involvement of stem-like populations with elevated ALDH1 in sarcomas for chemotherapeutic drug resistance

Honoki

Fujii²,

Kubo³

et al. 2010

Oncol Rep

122

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Abstract. Elevated aldehyde dehydrogenase 1 (ALDH1) has been proposed as one of the possible candidates for a stem cell maker that can be used for the isolation of cancer stem cells from cancers such as leukemia and breast cancer. In the current study, we found that subpopulations with elevated ALDH1 were present in the human sarcoma cell lines, MG63 (osteosarcoma) and HT1080 (fibrosarcoma), using Aldefluor assay. Both ALDH1 positive and negative cell populations were isolated from the MG63 cell line, by cell-sorting using FACSAria. Both subpopulations had a comparable ability to differentiate similarly to the parental MG63, under normal monolayer culture condition. Subpopulations with the ability to form spheres in anchorage-independent, serum-starved conditions showed increased ALDH1 mRNA expression in addition to strong mRNA expression of the stem cell-related genes, such as Nanog, Oct3/4, Stat3 and Sox2, and possessed ability for self-renewal with secondary sphere formation. Sarcosphere cells from the MG63 cell line showed strong chemo-resistance against both doxorubicin and cisplatin compared with monolayer, adherent cells. In conclusion, sphere-forming cells with elevated ALDH1 are a possible candidate for sarcoma stem cells, possessing strong chemoresistant capacities. Although ALDH1 elevation was not sufficient for representing sarcoma stem cells, the efficient detoxification could contribute to the chemo-resistant properties of the stem-like sphere cells form human sarcoma.

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Cellular levels of aldehyde dehydrogenases (ALDH1A1 and ALDH3A1) as predictors of therapeutic responses to cyclophosphamide-based chemotherapy of breast cancer: a retrospective study

Cited by 191 publications

References 23 publications

Identification of Staphylococcal Nuclease Domain-containing 1 (SND1) as a Metadherin-interacting Protein with Metastasis-promoting Functions

Identification of Staphylococcal Nuclease Domain-containing 1 (SND1) as a Metadherin-interacting Protein with Metastasis-promoting Functions

Impact of Smoking Cessation on Global Gene Expression in the Bronchial Epithelium of Chronic Smokers

Possible involvement of stem-like populations with elevated ALDH1 in sarcomas for chemotherapeutic drug resistance

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