Inactivation of MYO5B Promotes Invasion and Motility in Gastric Cancer Cells

Wu, Dong; Chen, Xiaobing; Chen, Ping; Yue, Dongli; Zhu, Linan; Fan, Qingxia

doi:10.1007/s10620-011-1989-z

Cited by 36 publications

(32 citation statements)

References 24 publications

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“…However both proteins were selectively expressed in the NEC cell lines, suggesting specific function in epithelial-like cells. The vesicle transport function of MYO5B may be coordinated by complex formation with RAB25 and/or RAB11A (r = 0.49) [85] (Figure 14). …”

Section: Resultsmentioning

confidence: 99%

Gene Expression Correlations in Human Cancer Cell Lines Define Molecular Interaction Networks for Epithelial Phenotype

et al. 2014

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Using gene expression data to enhance our knowledge of control networks relevant to cancer biology and therapy is a challenging but urgent task. Based on the premise that genes that are expressed together in a variety of cell types are likely to functions together, we derived mutually correlated genes that function together in various processes in epithelial-like tumor cells. Expression-correlated genes were derived from data for the NCI-60 human tumor cell lines, as well as data from the Broad Institute’s CCLE cell lines. NCI-60 cell lines that selectively expressed a mutually correlated subset of tight junction genes served as a signature for epithelial-like cancer cells. Those signature cell lines served as a seed to derive other correlated genes, many of which had various other epithelial-related functions. Literature survey yielded molecular interaction and function information about those genes, from which molecular interaction maps were assembled. Many of the genes had epithelial functions unrelated to tight junctions, demonstrating that new function categories were elicited. The most highly correlated genes were implicated in the following epithelial functions: interactions at tight junctions (CLDN7, CLDN4, CLDN3, MARVELD3, MARVELD2, TJP3, CGN, CRB3, LLGL2, EPCAM, LNX1); interactions at adherens junctions (CDH1, ADAP1, CAMSAP3); interactions at desmosomes (PPL, PKP3, JUP); transcription regulation of cell-cell junction complexes (GRHL1 and 2); epithelial RNA splicing regulators (ESRP1 and 2); epithelial vesicle traffic (RAB25, EPN3, GRHL2, EHF, ADAP1, MYO5B); epithelial Ca(+2) signaling (ATP2C2, S100A14, BSPRY); terminal differentiation of epithelial cells (OVOL1 and 2, ST14, PRSS8, SPINT1 and 2); maintenance of apico-basal polarity (RAB25, LLGL2, EPN3). The findings provide a foundation for future studies to elucidate the functions of regulatory networks specific to epithelial-like cancer cells and to probe for anti-cancer drug targets.

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Section: Resultsmentioning

confidence: 99%

Gene Expression Correlations in Human Cancer Cell Lines Define Molecular Interaction Networks for Epithelial Phenotype

et al. 2014

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“…Myo5b regulates membrane trafficking and cell polarity in association with Rab8 and Rab11, and downregulated expression of Rab11 and Myo5b has been linked to migration and invasion in gastric cancer. 48 Moreover, upregulation of its paralog Myo5a has been associated with malignant transformation in melanoma. 49 We also identified mutations in other steps of Rab-and Rac/Rho- .…”

Section: Discussionmentioning

confidence: 99%

Malignant pheochromocytomas/paragangliomas harbor mutations in transport and cell adhesion genes

et al. 2015

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One out of ten patients with pheochromocytoma (PCC) and paraganglioma (PGL) develop malignant disease. Today there are no reliable pathological methods to predict malignancy at the time of diagnosis. Tumors harboring mutations in the succinate dehydrogenase subunit B (SDHB) gene often metastasize but the sequential genetic events resulting in malignant progression are not fully understood. The aim of this study was to identify somatic mutations that contribute to the malignant transformation of PCC/PGL. We performed pair-wise (tumor-normal) whole-exome sequencing to analyze the somatic mutational landscape in five malignant and four benign primary PCC/sympathetic PGL (sPGL), including two biological replicates from each specimen. In total, 225 unique somatic mutations were identified in 215 genes, with an average mutation rate of 0.54 mutations/megabase. Malignant tumors had a significantly higher number of mutations compared to benign tumors (p < 0.001). Three novel genes were identified as recurrently mutated; MYCN, MYO5B and VCL, and mutations in these genes were exclusively found in malignant sPGL tumors. Mutations in the MYO5B gene could be verified in two publicly available data sets. A gene ontology analysis of mutated genes showed enrichment of cellular functions related to cytoskeletal protein binding, myosin complex and motor activity, many of which had functions in Rab and Rac/Rho GTPase pathways. In conclusion, we have identified recurrent mutations in genes related to intracellular transport and cell adhesion, and we have confirmed MYO5B to be recurrently mutated in PCC/PGL cases with malignant potential. Our study suggests that deregulated Rab and Rac/Rho pathways may be important in PCC/PGL tumorigenesis.Pheochromocytomas (PCCs) and paragangliomas (PGLs) are tumors derived from chromaffin cells of the adrenal medulla and extra-adrenal paraganglia. These tumors have a yearly incidence of two to eight per million inhabitants with a peak incidence in the third to fifth decades of life, and occur equally in males and females. 1,2 The proportion of patients that develop malignant disease is estimated to 10% although higher frequencies have been reported, particularly in PGL. 3 The definition of a malignant PCC/PGL is the presence of tumor metastases, 4 and patients with apparently benign

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“…MYO5A expression levels are increased in colorectal cancer in response to the transcription factor Snail [88], and it was suggested that its interaction with the pro-apoptotic protein Bmf, helps to prevent apoptosis as cells become less adhesive and invade the surrounding tissue. Decreased levels of MYO5B are associated with gastric cancer [89,90] and microvillus inclusion disease, a rare homozygous recessive disease [91]. Loss of MYO5B affects apical cargo protein transport in intestinal cells, which in turn causes intestinal brush border atrophy.…”

Section: Class 5 6 10 and 19 Myosin Isoformsmentioning

confidence: 99%

How myosin organization of the actin cytoskeleton contributes to the cancer phenotype

Peckham

2016

Biochemical Society Transactions

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The human genome contains 39 genes that encode myosin heavy chains, classified on the basis of their sequence similarity into 12 classes. Most cells express at least 12 different genes, from at least 8 different classes, which are typically composed of several class 1 genes, at least one class 2 gene, and classes 5, 6, 9, 10, 18 and 19. While the different myosin isoforms all have specific and non-overlapping roles in the cell, in combination they all contribute to the organisation of the actin cytoskeleton, and the shape and phenotype of the cell. Over (or under) expression of these different myosin isoforms can have strong effects on actin organisation, cell shape, and contribute to the cancer phenotype as discussed in this review.

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Inactivation of MYO5B Promotes Invasion and Motility in Gastric Cancer Cells

Abstract: The expression of MYO5B was downregulated in gastric cancer and inactivation of MYO5B may contribute to tumorigenesis. Therefore, MYO5B may become an important biomarker for gastric cancer in the future.

Cited by 36 publications

References 24 publications

Gene Expression Correlations in Human Cancer Cell Lines Define Molecular Interaction Networks for Epithelial Phenotype

Gene Expression Correlations in Human Cancer Cell Lines Define Molecular Interaction Networks for Epithelial Phenotype

Malignant pheochromocytomas/paragangliomas harbor mutations in transport and cell adhesion genes

How myosin organization of the actin cytoskeleton contributes to the cancer phenotype

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