Cell motility as a prognostic factor in Stage I nonsmall cell lung carcinoma

Shieh, Dar Bin; Godleski, John J.; Herndon, James E.; Azuma, Toshifumi; Mercer, Harriet; Sugarbaker, David J.; Kwiatkowski, David J.

doi:10.1002/(sici)1097-0142(19990101)85:1<47::aid-cncr7>3.0.co;2-l

Cited by 88 publications

(74 citation statements)

References 48 publications

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“…Lung cancer is one of the most frequent cancers in the world (Parker et al, 1997), and non-small cell lung cancer (NSCLC) represents 75-80% of all lung carcinomas (Shieh et al, 1999). The overall 5-year survival rate of these patients is only 15% (Nagamachi et al, 1998).…”

Section: Introductionsupporting

confidence: 75%

MALAT-1, a novel noncoding RNA, and thymosin β4 predict metastasis and survival in early-stage non-small cell lung cancer

et al. 2003

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Early-stage non-small cell lung cancer (NSCLC) can be cured by surgical resection, but a substantial fraction of patients ultimately dies due to distant metastasis. In this study, we used subtractive hybridization to identify gene expression differences in stage I NSCLC tumors that either did or did not metastasize in the course of disease. Individual clones (n ¼ 225) were sequenced and quantitative RT-PCR verified overexpression in metastasizing samples. Several of the identified genes (eIF4A1, thymosin b4 and a novel transcript named MALAT-1) were demonstrated to be significantly associated with metastasis in NSCLC patients (n ¼ 70). The genes' association with metastasis was stage-and histology specific. The Kaplan-Meier analyses identified MALAT-1 and thymosin b4 as prognostic parameters for patient survival in stage I NSCLC. The novel MALAT-1 transcript is a noncoding RNA of more than 8000 nt expressed from chromosome 11q13. It is highly expressed in lung, pancreas and other healthy organs as well as in NSCLC. MALAT-1 expressed sequences are conserved across several species indicating its potentially important function. Taken together, these data contribute to the identification of early-stage NSCLC patients that are at high risk to develop metastasis. The identification of MALAT-1 emphasizes the potential role of noncoding RNAs in human cancer.

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Section: Introductionsupporting

confidence: 75%

MALAT-1, a novel noncoding RNA, and thymosin β4 predict metastasis and survival in early-stage non-small cell lung cancer

et al. 2003

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“…Specifically in the late-stage subgroup, GSN overexpression was significantly correlated with the clinically defined platinum resistance based on PFI at 6 mo. This observation is consistent with a prognostic significance of GSN expression in non-small cell lung cancers (20) and oral cancer (21). Cellular GSN levels were found to be an important factor for tumor recurrence in highgrade tumors (22).…”

Section: Discussionmentioning

confidence: 99%

Cell fate regulation by gelsolin in human gynecologic cancers

Abedini

Wang

Huang

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Significance We tested the hypothesis that gelsolin (GSN) plays an important role in gynecological chemoresistance through the following: We provided strong evidence in support of GSN as an important etiologic factor in chemoresistance in vitro. We also determined the mechanism by which GSN exerts its prosurvival action. Our findings also suggest that the application of C-terminal GSN may represent a new therapeutic strategy for chemoresistant gynecologic cancer. We have also validated our in vitro findings with a clinical investigation that determines the relationship between GSN expression and cis -Diammine dichloroplatinium (II) sensitivity in human ovarian tumor. These findings agree with the notion that GSN plays a key role in the regulation of gynecological cell fate as reflected in chemoresistance.

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“…46 -48 Furthermore, the chemotactic cell migration of Ras-transformed NIH3T3 cells expressing the His321 mutant or human cytoplasmic gelsolin 25 toward fibronectin was also increased (Fujita et al, unpublished observation). Recently, Shieh et al 49 reported that high expression of gelsolin was a great risk factor for cancer recurrence in human nonsmall cell lung cancer. We observed, however, less recurrence of gelsolin transfectants in mice as judged by reappearance of tumor after an amputation.…”

Section: Discussionmentioning

confidence: 99%

Gelsolin functions as a metasatsis suppressor in B16-BL6 mouse melanoma cells and requirement of the carboxyl-terminus for its effect

et al. 2001

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Gelsolin, an actin-binding protein, is implicated as a critical regulator in cell motility. In addition, we have reported that cellular levels of gelsolin are decreased in various tumor cells, and overexpression of gelsolin by gene transfer suppresses tumorigenicity. We sought to assess the effects of gelsolin overexpression on metastasis and to determine the importance of a carboxyl-terminus that confers Ca 2؉ dependency on gelsolin for effects of its overexpression. Expression vectors with cDNA encoding either full-length wild-type or His321 mutant form, isolated from a flat revertant of Rastransformed cells and a carboxyl-terminal truncate, C-del of gelsolin, were transfected into a highly metastatic murine melanoma cell line, B16-BL6. Expression of introduced cDNA in transfectants was confirmed using Western blotting, 2-dimensional gel electrophoresis and reverse transcription-polymerase chain reaction (RT-PCR). We characterized phenotypes of transfectants, such as growth rate, colony formation in soft agar, cell motility and metastasis formation in vivo. Transfectants expressing the wild-type, His321 mutant and C-del gelsolin exhibited reduced growth ability in soft agar. Although expression of integrin ␤1 or ␣4 on the cell surface of transfectants was not changed, wild-type and His321 mutant gelsolin, except for C-del gelsolin, exhibited retardation of cell spreading, reduced chemotatic migration to fibronectin and suppressed lung colonization in spontaneous metastasis assay. Gelsolin may function as a metastasis suppressor as well as a tumor suppressor gene. The carboxylterminus of gelsolin is important for retardation of cell spreading, reduced chemotasis and metastasis suppression. © 2001 Wiley-Liss, Inc. Key words: gelsolin; metastasis; cell spreading; cell motilityMetastasis, the spread of malignant tumor cells from a primary site to distant sites, is the most life-threatening complication of cancer and a major problem of cancer treatment. 1,2 The metastatic process consists of multiple steps: (i) dissociation of tumor cell(s) from the primary site with a concomitant loss of cell-cell and cell-extracellular matrix (ECM) adhesions; (ii) tumor-cell adhesion to and subsequent local digestion of basement membrane; (iii) retraction of endothelial cells and subsequent intravasation; (iv) survival within the vasculature; (v) extravasation from vasculature at a distant site and (vi) growth in a "foreign" or ectopic organ environment. 3,4 Much attention has been paid to the interaction of cell-cell or cell-ECM adhesion [5][6][7] and to proteolysis by a variety of classes of degradative enzymes and their inhibitors, 8,9 even though tumor cell migration is also an essential step for establishment of cancer metastasis. It is well known that the actin cytoskeleton is a major component of the cell motility machinery. 10,11 Evidence is accumulating that changes in actin cytoskeletal organization, adhesiveness and motility are important not only for tumor development and progression but also may be critical for deter...

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Cell motility as a prognostic factor in Stage I nonsmall cell lung carcinoma

Cited by 88 publications

References 48 publications

MALAT-1, a novel noncoding RNA, and thymosin β4 predict metastasis and survival in early-stage non-small cell lung cancer

MALAT-1, a novel noncoding RNA, and thymosin β4 predict metastasis and survival in early-stage non-small cell lung cancer

Cell fate regulation by gelsolin in human gynecologic cancers

Gelsolin functions as a metasatsis suppressor in B16-BL6 mouse melanoma cells and requirement of the carboxyl-terminus for its effect

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