Actinin-4 increases cell motility and promotes lymph node metastasis of colorectal cancer

Honda, Kazufumi; Yamada, Tesshi; Hayashida, Yasuharu; Idogawa, Masashi; Sato, Satoshi; Hasegawa, Fumio; Ino, Yoshinori; Ono, M.; Hirohashi, Setsuo

doi:10.1053/j.gastro.2004.10.004

Cited by 191 publications

(213 citation statements)

References 30 publications

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“…10,29 Other primary antibodies used were anti-E-cadherin (clone NCH-38, 1:100, Dako, Glostrup, Denmark) and anti-b-catenin (rabbit polyclonal, ready-to-use, Lab Vision).…”

Section: Tma and Immunohistochemistry (Ihc)mentioning

confidence: 99%

“…We categorized the cytoplasmic and membranous reaction together, because actinin-4 has been shown to elicit its capacity for enhancing cell motility by bundling the actin-cytoskeleton located at the inner surface of the cytoplasm, where actinin-4 being highly concentrated in membrane ruffles, and also because distinction between cytoplasmic and membranous expression is often difficult in tumor cells with scant cytoplasm. 9,10 Cell membranous immunoreactivity was used as a reactive parameter for both E-cadherin and b-catenin, and nuclear immunoreactivity was also assessed for b-catenin. On the basis of the previous report, membranous immunoreactivity with both anti-E-cadherin and anti-b-catenin antibodies was scored according to the presence and extent of the immunoreaction, then divided into reduced and preserved groups according to whether immunoreactive tumor cells comprised o50% or Z50% of the total cancer cell population in each core.…”

Section: Evaluation Of Ihcmentioning

confidence: 99%

“…9 The actinin-4 protein is highly concentrated at the leading edge of the cytoplasm of motile cells or actively moving structures such as cell-surface ruffles. [9][10][11][12] The cytoplasmic expression levels of actinin-4 are significantly increased in cells exhibiting enhanced motility. 9,10 Increased cytoplasmic expression of actinin-4 is reportedly associated with histologically invasive phenotypes of breast cancer, poor prognosis of breast and non-small cell lung cancers, and lymph node metastasis of colorectal cancer.…”

mentioning

confidence: 99%

“…[9][10][11][12] The cytoplasmic expression levels of actinin-4 are significantly increased in cells exhibiting enhanced motility. 9,10 Increased cytoplasmic expression of actinin-4 is reportedly associated with histologically invasive phenotypes of breast cancer, poor prognosis of breast and non-small cell lung cancers, and lymph node metastasis of colorectal cancer. 9,10,13 Notably, Honda et al 9 have also reported the expression of actinin-4 in the nucleus of several cancer cell lines and some low-infiltrative histological subtypes of breast cancer.…”

mentioning

confidence: 99%

“…9,10 Increased cytoplasmic expression of actinin-4 is reportedly associated with histologically invasive phenotypes of breast cancer, poor prognosis of breast and non-small cell lung cancers, and lymph node metastasis of colorectal cancer. 9,10,13 Notably, Honda et al 9 have also reported the expression of actinin-4 in the nucleus of several cancer cell lines and some low-infiltrative histological subtypes of breast cancer. This nuclear expression was shown to result from translocation of actinin-4 induced by phosphatidylinositol 3-kinase (PI3-K) inhibitor or by cytochalasin D, which inhibits actin polymerization.…”

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confidence: 99%

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Actinin-4 expression in ovarian cancer: a novel prognostic indicator independent of clinical stage and histological type

Yamamoto

Tsuda

Honda³

et al. 2007

Modern Pathology

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Actinin-4 is an isoform of non-muscular a-actinin and actin-bundling protein. By enhancing cell motility, actinin-4 shows different biological properties from another isoform of non-muscular actinin 'actinin-1' and variable clinicopathological implications of actinin-4 have been demonstrated in some human malignancies such as breast cancers, lung cancers, and colorectal cancers. We herein described the clinicopathological and prognostic significance of actinin-4 expression in ovarian cancers. Actinin-4 expression was analyzed immunohistochemically in 265 primary ovarian carcinomas: 116 serous, 71 clear cell, 43 endometrioid, and 35 mucinous adenocarcinomas. With reference to endothelial immunoreactivity, cytoplasmic expression of actinin-4 was classified as either low (including negative) or high. Then, various parameters such as patients' characteristics, histopathological findings including E-cadherin and b-catenin immunoreactivity, and clinical outcome, were compared between groups showing differences in the intensity or intracellular distribution of actinin-4 immunoreactivity. High expression of actinin-4 was demonstrated in 137 (57%) cases and was associated with serous histology (P ¼ 0.0075), high histological grade (Po0.0001), an advanced disease stage (P ¼ 0.036), a high degree of residual disease after initial surgery (P ¼ 0.0047), poor patient outcome (5-year survival: 52.4% in the high-expression group vs 71.9% in the low expression group, P ¼ 0.0043 by log-rank test), and also with reduced E-cadherin and preserved b-catenin expressions (P ¼ 0.0097 and 0.017, respectively). Nuclear immunoreactivity for actinin-4 was detected in 20 (7.5%) cases and was associated with low histological grade (P ¼ 0.0079) but not with other variables. Multivariate analysis showed that high actinin-4 expression was an independent prognostic factor for overall survival, as well as a high degree of residual disease and clear-cell histology. Accumulation of actinin-4 in the cytoplasm may be related to a higher propensity for tumor invasiveness and metastasis, probably by enhancing cell motility, and could be a novel prognostic indicator for patients with ovarian carcinomas.

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“…10,29 Other primary antibodies used were anti-E-cadherin (clone NCH-38, 1:100, Dako, Glostrup, Denmark) and anti-b-catenin (rabbit polyclonal, ready-to-use, Lab Vision).…”

Section: Tma and Immunohistochemistry (Ihc)mentioning

confidence: 99%

Section: Evaluation Of Ihcmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Actinin-4 expression in ovarian cancer: a novel prognostic indicator independent of clinical stage and histological type

Yamamoto

Tsuda

Honda³

et al. 2007

Modern Pathology

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Prospective study of routine contrast radiology after total gastrectomy

Lamb

Griffin

Chandrashekar

et al. 2004

British Journal of Surgery

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WAVE2 is associated with poor prognosis in pancreatic cancers and promotes cell motility and invasiveness via binding to ACTN4

et al. 2018

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WAVE2 is a member of the WASP/WAVE family of actin cytoskeletal regulatory proteins; unfortunately, little is known about its function in pancreatic cancers. In this study, we report the role of WAVE2 in the motility and invasiveness of pancreatic cancer cells. High WAVE2 expression in human pancreatic cancer tissues was correlated with overall survival. WAVE2 accumulated in the cell protrusions of pancreatic cancer cell lines. Downregulation of WAVE2 by small interfering RNA decreased the cell protrusions and inhibited the motility and invasiveness of pancreatic cancer cells. WAVE2 promoted pancreatic cancer cell motility and invasion by forming a complex with the actin cytoskeletal protein alpha‐actinin 4 (ACTN4). Downregulation of ACTN4 by small interfering RNA also inhibited the motility and invasiveness of the cells through a decrease in cell protrusions. Further investigation showed that WAVE2/ACTN4 signaling selectively stimulated p27 phosphorylation and thereby increased the motility and invasiveness of the cells. These results suggest that WAVE2 and ACTN4 stimulate p27 phosphorylation and provide evidence that WAVE2 promotes the motility and invasiveness of pancreatic cancer cells.

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Actinin-4 increases cell motility and promotes lymph node metastasis of colorectal cancer

Cited by 191 publications

References 30 publications

Actinin-4 expression in ovarian cancer: a novel prognostic indicator independent of clinical stage and histological type

Actinin-4 expression in ovarian cancer: a novel prognostic indicator independent of clinical stage and histological type

Prospective study of routine contrast radiology after total gastrectomy

WAVE2 is associated with poor prognosis in pancreatic cancers and promotes cell motility and invasiveness via binding to ACTN4

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