Possible mechanism of metastasis in lung adenocarcinomas with a micropapillary pattern

Miyoshi, Tatsu; Shirakusa, Takayuki; Ishikawa, Yuichi; Iwasaki, Atsushi; Shiraishi, Takeshi; Makimoto, Yoshifumi; Iwasaki, Hiroshi; Nabeshima, Kazuki

doi:10.1111/j.1440-1827.2005.01847.x

Cited by 38 publications

(26 citation statements)

References 18 publications

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“…The relationship between the presence of MPC and the lymph node metastasis has been demonstrated [37,38]. MPC has been demonstrated to associate with an abnormality of an adhesion molecule in the cadherin-catenin-actin network, and with the detachment of cells from the stroma by the presence of MUC1 in the stroma-facing surface of MPC.…”

Section: Discussionmentioning

confidence: 97%

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Expression of minichromosome maintenance 7 (MCM7) in small lung adenocarcinomas (pT1): Prognostic implication

et al. 2009

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Minichromosome maintenance (MCM) proteins, essential molecules in the initiation and elongation of DNA replication, have been considered to be good indicators of cell proliferation. We examined the expressions of MCM7 and Ki-67 in lung adenocarcinomas (ACs) with a diameter less than 3cm (pT1), to clarify their pathobiological significance. Immunohistochemistry was conducted to obtain labeling indices (LIs%) for MCM7, MCM2 and Ki-67 in 100 surgically removed pT1 ACs. The LIs were compared with clinicopathological profiles and overall survival rates. The mean LIs of MCM7 and Ki-67 were 20.2+/-15.2% and 13.7+/-11.2%, the value being higher in the former than in the latter (P<0.01). MCM7 LIs were significantly correlated with sex, histological grade, histological subtype, tumor size, LIs of Ki-67, MCM2 and P53 (P<0.05). LIs of MCM7 and Ki-67 were significantly higher in the 84 non-bronchioloalveolar carcinomas than in the 16 bronchioloalveolar carcinomas (P<0.01). Kaplan-Meier survival curves showed that patients with higher MCM7 LIs had poorer prognosis in the 100 pT1 ACs as well as in the 73 stage I ACs. Multivariate Cox regression analysis confirmed that the LIs of MCM7, but not the LIs of MCM2 and Ki-67, was an independent prognostic marker in the 73 stage I ACs. These results suggest that MCM7 is an independent prognostic marker, being more reliable than MCM2 or Ki-67 in human pT1 ACs as well as in human stage I ACs.

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Section: Discussionmentioning

confidence: 97%

“…MPC in lung cancer was first reported in 2002, and has been reported to have an unfavorable biological behavior, and that the patients with MPC tend to present with advanced stage including lymph node metastasis [29,37]. The relationship between the presence of MPC and the lymph node metastasis has been demonstrated [37,38].…”

Section: Discussionmentioning

confidence: 98%

Expression of minichromosome maintenance 7 (MCM7) in small lung adenocarcinomas (pT1): Prognostic implication

et al. 2009

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“…Recently, this adenocarcinoma variant has also been described in patients with lung adenocarcinomas. [5][6][7][8][9][10][11][12][13][14] However, the most recent World Health Organization (WHO) classifi cation makes only brief reference to the micropapillary pattern. 15 This report presents a series of 15 resected cases of lung adenocarcinoma with micropapillary components.…”

Section: Introductionmentioning

confidence: 99%

Lung adenocarcinomas with micropapillary components

Maeda

Isowa

Onuma

et al. 2009

Gen Thorac Cardiovasc Surg

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“…Protein analyses substantiate involvement of IQGAP1 in tumorigenesis. For example, IQGAP1 protein is overexpressed * This work was supported in part by a grant from the National Institutes of in several human neoplasms, including gastric (16), colorectal (20), lung (21), ovary (22), and liver (23). In addition, the subcellular location of IQGAP1 is altered in neoplasia.…”

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confidence: 99%

IQGAP1 Stimulates Proliferation and Enhances Tumorigenesis of Human Breast Epithelial Cells

Jadeski

Mataraza

Jeong

et al. 2008

Journal of Biological Chemistry

130

143

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The scaffold protein IQGAP1 integrates signaling pathways and participates in diverse cellular activities. IQGAP1 is overexpressed in a number of human solid neoplasms, but its functional role in tumorigenesis has not been previously evaluated. Here we report that IQGAP1 contributes to neoplastic transformation of human breast epithelial cells. The amount of IQGAP1 in breast carcinoma is greater than that in normal tissue, with highly metastatic breast epithelial cells expressing the highest levels. Overexpression of IQGAP1 enhances proliferation of MCF-7 breast epithelial cells. Reduction of endogenous IQGAP1 by RNA interference impairs both serum-dependent and anchorage-independent growth of MCF-7 cells. Consistent with these in vitro observations, immortalized MCF-7 cells overexpressing IQGAP1 form invasive tumors in immunocompromised mice, whereas tumors derived from MCF-7 cells with stable knockdown of IQGAP1 are smaller and less invasive. In vitro analysis with selected IQGAP1 mutant constructs and a chemical inhibitor suggests that actin, Cdc42/Rac1, and the mitogen-activated protein kinase pathway contribute to the mechanism by which IQGAP1 increases cell invasion. Collectively, our data reveal that IQGAP1 enhances mammary tumorigenesis, suggesting that it may be a target for therapeutic intervention.Tumor progression that culminates in clinically relevant metastatic lesions is the end point of a complex sequence of interrelated cellular events. After the initial transforming event, tumor cell proliferation, invasion, and migration, as well as vascularization of the tumor mass, occur. A thorough understanding of the molecular mechanisms that regulate tumor progression will provide the biological foundation for improving the efficacy of current therapeutic interventions (1-3).IQGAP1 is a 189-kDa scaffolding protein that contains multiple protein-interacting domains (for reviews see Refs. 4 -7). These include a calponin homology domain, a polyprolinebinding domain, four calmodulin-binding motifs, and a Ras-GAP-related domain. The motifs present in IQGAP1 are involved in the interaction of IQGAP1 with specific proteins, such as actin, calmodulin, members of the Rho GTPase family (i.e. Rac1 and Cdc42), Rap1, E-cadherin, ␤-catenin, members of the mitogen-activated protein kinase (MAPK) 4 pathway, and adenomatous polyposis coli (7,8). By interacting with these proteins, IQGAP1 regulates multiple fundamental cellular activities including cytoskeletal organization, cell-cell adhesion, cell migration, transcription, and signal transduction. For example, binding of IQGAP1 to ␤-catenin both disrupts the E-cadherin-catenin complex, inhibiting epithelial cell-cell adhesion (9), and increases ␤-catenin-mediated transcriptional activation (10). IQGAP1 increases active Cdc42 in mammalian cells, resulting in formation of actin filopodia and microspikes (11), and promotion of cell migration and invasion (12). These morphological and functional changes are not observed with a mutant IQGAP1 construct with impeded Cdc42-me...

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Possible mechanism of metastasis in lung adenocarcinomas with a micropapillary pattern

Cited by 38 publications

References 18 publications

Expression of minichromosome maintenance 7 (MCM7) in small lung adenocarcinomas (pT1): Prognostic implication

Expression of minichromosome maintenance 7 (MCM7) in small lung adenocarcinomas (pT1): Prognostic implication

Lung adenocarcinomas with micropapillary components

IQGAP1 Stimulates Proliferation and Enhances Tumorigenesis of Human Breast Epithelial Cells

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