Reactivation of<i>MASPIN</i>in non-small cell lung carcinoma (NSCLC) cells by artificial transcription factors (ATFs)

Beltran, Adriana S.; Blancafort, Pilar

doi:10.4161/epi.6.2.13700

Cited by 44 publications

(53 citation statements)

References 61 publications

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“…These studies have been supported using in vitro and in vivo models of lung cancer. Beltran and colleagues (31) demonstrated that restoration of maspin expression in NSCLC cells using artificial transcription factors combined with chromatin modifier compounds, reduced NSCLC metastatic behavior (31). Maspin was also shown to be involved in regulating the survival of lung cancer cells to chemotherapy drugs (32).…”

Section: Discussionmentioning

confidence: 99%

TUBB3/βIII-Tubulin Acts through the PTEN/AKT Signaling Axis to Promote Tumorigenesis and Anoikis Resistance in Non–Small Cell Lung Cancer

et al. 2015

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bIII-tubulin (encoded by TUBB3) expression is associated with therapeutic resistance and aggressive disease in non-small cell lung cancer (NSCLC), but the basis for its pathogenic influence is not understood. Functional and differential proteomics revealed that bIII-tubulin regulates expression of proteins associated with malignant growth and metastases. In particular, the adhesionassociated tumor suppressor maspin was differentially regulated by bIII-tubulin. Functionally, bIII-tubulin suppression altered cell morphology, reduced tumor spheroid outgrowth, and increased sensitivity to anoikis. Mechanistically, the PTEN/AKT signaling axis was defined as a critical pathway regulated by bIII-tubulin in NSCLC cells. bIII-Tubulin blockage in vivo reduced tumor incidence and growth. Overall, our findings revealed how bIII-tubulin influences tumor growth in NSCLC, defining new biologic functions and mechanism of action of bIII-tubulin in tumorigenesis.Cancer Res; 75(2); 415-25. Ó2014 AACR.

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Section: Discussionmentioning

confidence: 99%

TUBB3/βIII-Tubulin Acts through the PTEN/AKT Signaling Axis to Promote Tumorigenesis and Anoikis Resistance in Non–Small Cell Lung Cancer

et al. 2015

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“…High frequency of co-expression of maspin and p63, as well as maspin and p53, has been detected in squamous cell carcinoma (28). Restoration of maspin expression suppresses cell invasion in NCSLC cells (29).…”

Section: Introductionmentioning

confidence: 99%

Different maspin functions in the lung adenocarcinoma A549 and SPC-A1 cell lines

Zhou

Qin

Zhou

et al. 2015

International Journal of Molecular Medicine

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Abstract. Mammary serine protease inhibitor (maspin) is a tumor suppressor gene that is silenced in the majority of cancer cells during metastatic progression by transcriptional and epigenetic mechanisms. The function of maspin in non-small cell lung cancer cells (NSCLC) has not been clearly defined. In the present study, the expression of maspin in NSCLC cell lines, in particular, the adenocarcinoma cell lines, was heterogeneous. While the expression levels of maspin in PC-9 and H460 cell lines were intact, the expression of maspin in the A549 and SPC-A1 cells was hardly detected. Ectopic expression of maspin in A549 cells carrying the K-ras gene point mutation significantly inhibited cell migration and invasion abilities, which was associated with downregulated expression of matrix metalloproteinase-2 and integrin β1. Ectopic expression of maspin in SPC-A1 cells harboring the wild-type K-ras gene predominantly affected cell growth via targeting the AKT signaling molecules. Maspin functions differently in lung adenocarcinoma cells, possibly due to the varied molecular characteristics. IntroductionLung cancer is a leading cause of cancer mortality worldwide. Lung cancer is generally divided into non-small cell lung cancer cells (NSCLC) and SCLC, in which the NSCLC constitutes 80-85% of lung cancers. The three major NSCLC subtypes are adenocarcinoma, squamous cell carcinoma and large cell carcinoma. NSCLC, which is characterized by slow tumor cell growth and dissemination, is refractory to chemotherapy and chest radiotherapy. Several driven genes have been identified in NSCLC, such as EGFR, c-MET and the ALK-EML4 fusion gene (1). Treatment for lung cancer is mainly based on tumor stage, tumor pathology and molecular pathology. Understanding thoroughly the molecular mechanism underlying the aberrant cellular events driving lung cancer progressions is crucial for developing novel treatments.Mammary serine protease inhibitor (maspin), also known as Serpin B5, was first identified in 1994 (2). Maspin belongs to the serine protease inhibitor superfamily, and is predominantly localized in the cytoplasm, but is also localized in the nucleus and membrane, and is secreted. The exact roles of maspin in cancer are far more complicated than initially thought due to the conflicting experimental and clinical data that have been reported. In prostate cancer, the expression of maspin is frequently absent (3). Overexpression of maspin is considered an independent factor in predicting a favorable prognosis in breast cancer and lung squamous cell cancer (4-6). However, it has been also reported that the increased nuclear maspin expression predicts a favorable prognosis, whereas the enhanced cytoplasmic expression is associated with early-relapsing and unfavorable prognosis in breast cancer (7). Enhanced expression of maspin is correlated with unfavorable prognosis in pancreatic, ovarian and colorectal cancer (8-10). High maspin expression correlates with an unfavorable outcome in colorectal cancer in stage III and IV, suggesting th...

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“…ATFs consist of DNA-binding domains, specifically engineered to recognize a sequence of interest, such as zinc fingers (ZFs), 15 fused to transcriptional activation or repression domains, such as VP64 (four copies of the viral protein VP16) or super KRAB domain (SKD), respectively. 16 Such ATFs have previously been shown by us 17,18 and others 19,20 to effectively up-or downregulate genes both in vitro and in vivo, including epigenetically silenced genes and including ICAM-1. 20 In this study, ATFs were exploited to determine the cellbiological role of ICAM-1 in ovarian cancer.…”

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confidence: 99%

Upregulation of endogenous ICAM‐1 reduces ovarian cancer cell growth in the absence of immune cells

Groote

Kazemier

Huisman

et al. 2013

Intl Journal of Cancer

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Ovarian cancer is a difficult-to-treat cancer with a 5-year survival rate of only~45%, due to late diagnosis and therapy resistance. In need of new therapeutic approaches, induction of intercellular adhesion molecule (ICAM)-1 expression might be of interest, since the expression of ICAM-1 is lower in ovarian cancer cells compared with healthy ovarian cells and correlated with decreased tumorigenicity. Whereas ICAM-1 expression on tumor cells is of importance for attracting immune cells, ICAM-1 might also induce tumorigenicity and chemoresistance. In ovarian cancer, such a role of ICAM-1 is unclear. Here, we investigated whether ICAM-1 has a cell-biological role by bidirectional modulation of ICAM-1 expression using ICAM-targeting artificial transcription factors. For a panel of ovarian cancer cells, tumor growth and cisplatin sensitivity were evaluated. Induction of ICAM-1 expression (ranging from 3-to 228-fold on mRNA level and 1.7-to 108-fold on protein level) resulted in indications of decreased ovarian cancer cell growth and reduced cisplatin sensitivity. Repression ranged from 48 to 94% on mRNA level and 47 to 91% on protein level. This study shows that, next to its established immunogenic role, ICAM-1 affects cell biological behavior of ovarian cancer cells and, importantly, that reexpression by artificial transcription factors represents a powerful approach for functional validation of genes epigenetically silenced in cancer, such as ICAM-1.

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Reactivation ofMASPINin non-small cell lung carcinoma (NSCLC) cells by artificial transcription factors (ATFs)

Cited by 44 publications

References 61 publications

TUBB3/βIII-Tubulin Acts through the PTEN/AKT Signaling Axis to Promote Tumorigenesis and Anoikis Resistance in Non–Small Cell Lung Cancer

TUBB3/βIII-Tubulin Acts through the PTEN/AKT Signaling Axis to Promote Tumorigenesis and Anoikis Resistance in Non–Small Cell Lung Cancer

Different maspin functions in the lung adenocarcinoma A549 and SPC-A1 cell lines

Upregulation of endogenous ICAM‐1 reduces ovarian cancer cell growth in the absence of immune cells

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