Tumor Metastasis-Associated Human Mtal Gene: Role in Epithelial Cancer Cell Proplieration and Regulation

Nicolson, Garth L.; Nawa, Akihiro; Toh, Yasushi; Taniguchi, Shigeki; Nishimori, Katsuhiko

doi:10.1007/0-306-47821-8_3

Cited by 61 publications

(91 citation statements)

References 36 publications

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“…Toh et al reported that the MTA1 protein is associated with histone deacetylation in vitro (13) and in clinical sample of human cancers (14). The MTA1 protein may serve multiple functions in cellular signaling, chromosome remodeling and transcription processes that are important in the progression, invasion and growth of metastatic epithelial cells (15). The overexpression of MTA1 protein and acetylation level of histone H4 protein, both of which are closely related, might be useful predictors of malignant potential of esophageal squamous cell carcinomas (14).…”

Section: Discussionmentioning

confidence: 99%

Overexpression of Metastatic Tumor Antigen in Osteosarcoma: Comparison between Conventional High-Grade and Central Low-Grade Osteosarcoma

et al. 2005

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Section: Discussionmentioning

confidence: 99%

Overexpression of Metastatic Tumor Antigen in Osteosarcoma: Comparison between Conventional High-Grade and Central Low-Grade Osteosarcoma

et al. 2005

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“…Despite the important role of MMP-2 in NSCLC, it is interesting to note that MMP-2 was not found in human SCLC, 42 which may indicate distinct strategies of invasion being used by these 2 types of lung cancer. Future studies investigating a potential role for the histone deacetylase metastasisassociated (MTA1) gene product, 43 as well as other metastasisassociated genes (e.g., mst1, nm23, KiSS1, MKK4, galectin-3, etc.) among the DLKP variants, may help to fully elucidate their mechanism(s) of drug-induced in vitro invasiveness.…”

Section: Discussionmentioning

confidence: 99%

Enhanced in vitro invasiveness and drug resistance with altered gene expression patterns in a human lung carcinoma cell line after pulse selection with anticancer drugs

Liang

O’Driscoll

McDonnell

et al. 2004

Intl Journal of Cancer

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The human lung carcinoma cell line DLKP was exposed to sequential pulses of 10 commonly used chemotherapeutic drugs (VP-16, vincristine, taxotere, mitoxantrone, 5-fluorouracil, methotrexate, CCNU, BCNU, cisplatin and chlorambucil); resulting cell lines exhibited resistance to the selecting agents (ranging approx. 1.5-to 36-fold) and, in some cases, cross-resistance to methotrexate (approx. 1.4-to 22-fold), vincristine (1.6-to 262-fold), doxorubicin (Adriamycin, approx. 1.1-to 33-fold) and taxotere (approx. 1.1-to 36-fold). Several of the variants displayed collateral sensitivity to cisplatin. A marked increase in in vitro invasiveness and motility was observed with variants pulsed with mitoxantrone, 5-fluorouracil, methotrexate, BCNU, cisplatin and chlorambucil. There was no significant change in invasiveness of cells pulsed with VP-16, vincristine, taxotere or CCNU. All of the pulseselected variants showed elevated levels of MDR-1/P-gp protein by Western blot analysis, although mdr-1 mRNA levels were not increased (except for DLKP-taxotere). In DLKPtaxotere, MRP1 protein levels were also greatly elevated, but mrp1 mRNA levels remained unchanged. BCRP was upregulated in DLKP-mitoxantrone at both the mRNA and protein levels. Gelatin zymography, Western blot and RT-PCR showed that DLKP and its variants secreted MMPs 2, 9 and 13. MMP inhibition assays suggested that MMP-2 plays a more important role than MMPs 9 and 13 in cell invasion of these DLKP drug-resistant variants in vitro. Reducing intracellular drug levels, often associated with overexpression of P-gp, 3 members of the MRP family 4 and the BCRP/ MXR protein, 5 is an important and frequent mechanism of MDR.Invasion through basement membrane is believed to be a critical step in metastasis. There are 4 main classes of proteases involved in proteolytic degradation of the ECM: serine-, cysteine-and aspartyl-proteases as well as MMPs. 6 The MMPs are a family of more than 20 members produced by tumour cells, connective tissue cells and inflammatory cells. MMPs are secreted as latent proenzymes and activated by proteolytic removal of an aminoterminal domain. 7 A large body of evidence shows that MMPs play a crucial role in cancer invasion and metastasis. Based on sequence homology and substrate specificity, MMP-2 and MMP-9 are classified as type IV collagenases that degrade the major component (type IV collagen) of basement membrane; 8 MMP-13, also called "collagenase-3", belongs to a group known as interstitial collagenases, which degrade collagen types I, II, III, VII, VIII and X. 9 The possibility of a relationship between drug resistance and invasion/metastasis phenotypes has been raised by 2 types of observation: 10 firstly, some tumour cells selected for resistance to drugs are invasive/metastatic relative to nonresistant parental cells; secondly, in some cases, secondary (more metastatic) tumours are more resistant to chemotherapeutic drugs than their primary counterparts. In support of this, Osmak et al. 11 reported a study of drug-resistant cervical and ...

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“…A large body of work suggests a role for MTA1 in human cancer (2,36,37) as well as a critical contribution of the loss of PTEN in cell survival signaling (38 -40). Earlier studies have demonstrated that MTA1 forms a corepressor complex with HDAC1/2 and is recruited to the target gene promoters, thereby repressing gene transcription (29).…”

Section: Mta1 Expression Inversely Correlates With Pten Expresmentioning

confidence: 99%

Metastasis-associated Protein 1/Histone Deacetylase 4-Nucleosome Remodeling and Deacetylase Complex Regulates Phosphatase and Tensin Homolog Gene Expression and Function

Reddy

Pakala

Molli

et al. 2012

Journal of Biological Chemistry

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Background: MTA1 is overexpressed in several advanced cancers, but its role in cell survival signaling is yet to be elucidated. Results: MTA1 transcriptionally represses the expression of PTEN and, consequently, PTEN-dependent signaling and functions. Conclusion: PTEN is a target of the MTA1/HDAC4-containing NuRD complex. Significance: This study provides a novel mechanistic insight into the regulation of PTEN by MTA1.

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Tumor Metastasis-Associated Human Mtal Gene: Role in Epithelial Cancer Cell Proplieration and Regulation

Cited by 61 publications

References 36 publications

Overexpression of Metastatic Tumor Antigen in Osteosarcoma: Comparison between Conventional High-Grade and Central Low-Grade Osteosarcoma

Overexpression of Metastatic Tumor Antigen in Osteosarcoma: Comparison between Conventional High-Grade and Central Low-Grade Osteosarcoma

Enhanced in vitro invasiveness and drug resistance with altered gene expression patterns in a human lung carcinoma cell line after pulse selection with anticancer drugs

Metastasis-associated Protein 1/Histone Deacetylase 4-Nucleosome Remodeling and Deacetylase Complex Regulates Phosphatase and Tensin Homolog Gene Expression and Function

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