Cell cycle regulated phosphorylation of LIMD1 in cell lines and expression in human breast cancers

Huggins, Christopher J.; Andrulis, Irene L.

doi:10.1016/j.canlet.2008.03.015

Cited by 34 publications

(38 citation statements)

References 19 publications

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“…Their data suggests that LIMD1 is not mutated or deleted in the majority of breast cancers. More recently the same group have demonstrated that 80% (16/20) of breast cancers have unchanged levels of LIMD1 mRNA compared to controls 35 and this supports our findings that LIMD1 was present and expressed in all breast cancer samples tested. Our findings would suggest that it is the regulation of LIMD1 protein levels, perhaps by epigenetic regulation that account for differential expression.…”

Section: Discussionsupporting

confidence: 91%

“…Our findings would suggest that it is the regulation of LIMD1 protein levels, perhaps by epigenetic regulation that account for differential expression. However, the preliminary pilot study by Huggins and Andrulis, 35 where they compared the LIMD1 promoter methylation status in 4 breast cancer samples with LIMD1 mRNA, indicated that the degree of FIGURE 4 -A Kaplan-Meier plot measuring patient survival time in months against cumulative survival for nuclear LIMD1 staining. Staining was categorised into 3 groups; strong, moderate and weak/no staining (which have been culminated).…”

Section: Discussionmentioning

confidence: 99%

“…Such staining patterns support previous studies showing LIMD1 family members localising to the cytosol 19,34 and more recently LIMD1 itself localised to the nucleus. 35 In contrast LIMD1 was not present in foam cells or the surrounding stroma of the breast (Fig. 1).…”

Section: Limd1 Expression In Normal Breast Tissuementioning

confidence: 92%

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Differential subcellular localisation of the tumour suppressor protein LIMD1 in breast cancer correlates with patient survival

Spendlove¹,

Al‐Attar²,

Watherstone³

et al. 2008

Intl Journal of Cancer

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The tumour suppressor gene (TSG) LIM domain containing protein 1 (LIMD1) has been associated with transformation of epithelial cells of the lung and its expression is downregulated in all lung tumour samples tested compared to normal lung matched controls. In the first study of its kind we used an anti-LIMD1 specific monoclonal antibody to investigate expression/localisation of the LIMD1 protein in a well-characterised tissue microarray of breast cancers and normal adjacent epithelia. Comparison of tumour with adjacent normal and distant normal tissue demonstrated that LIMD1 expression is moderate to high compared to tumour. There was also a significant correlation with histological grade (p 5 0.0001), tumour size (p 5 0.013) and tumour type (p 5 0.004) indicating an association with aggressive disease. Cytoplasmic LIMD1 expression was seen in 99.3% of cases, with 43.1% showing both nuclear and cytoplasmic localisation. Absence/loss of nuclear staining showed a strong correlation with patient survival and was indicative of poor prognosis (p 5 0.033). There was no association with lymph node status and other clinicopathological parameters. Nuclear staining was more pronounced in better prognosis tumours and normal tissue. This study demonstrates that LIMD1 represents a novel prognostic marker for breast cancer. Combined with the fact that LIMD1 expression is downregulated in lung cancers this clearly indicates that LIMD1 may represent a critical TSG, the function of which is deregulated via overall loss of expression and/or relocalisation within the cell during tumour development. The possible functions of LIMD1 localisation within the nucleus and cytoplasm and its relationship to tumour prognosis are discussed. ' 2008 Wiley-Liss, Inc.Key words: LIMD1; Ajuba; breast cancer; E-cadherin; tissue microarray; prognostic indicator Breast cancer is the most common cause of cancer-related death in women in the western world. Alterations in tumour suppressor genes (TSG) and oncogenes are common causes for the higher proliferative rates and pathogenic characteristics associated with tumour development. Cytogenetics and allelotyping have shown that allelic loss from several distinct regions on chromosome 3p, including 3p25, 3p21-22, 3p21.3, 3p12-13 and 3p14, are the earliest and most frequent genomic abnormalities involved in a wide spectrum of major epithelial cancers of lung 1-6 and breast tissues 7-9 as well as many other epithelial derived cancers. [10][11][12][13] Specifically the 3p21.3 gene cluster contains many TSG and oncogenes and is a region of major loss of heterozygosity in lung cancers. [14][15][16] Abnormalities at the 3p21.3 chromosomal region include homozygous deletions, loss of heterozygosity and expressional deficiencies that can be induced through methylation of promoters, altered mRNA transcripts and loss of protein translocation. 17 The chromosome 3 commonly eliminated region (C3CER1) is located within the 3p21.3 gene cluster. The C3CER1 contains several putative TSG and is eliminated in many forms o...

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

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Differential subcellular localisation of the tumour suppressor protein LIMD1 in breast cancer correlates with patient survival

Spendlove¹,

Al‐Attar²,

Watherstone³

et al. 2008

Intl Journal of Cancer

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“…In the cytoplasm, LIMD1 colocalises with focal adhesions (Huggins and Andrulis, 2008;Petit et al, 2005), adherens junctions (Das Thakur et al, 2010) and mRNA processing bodies (P-bodies) (James et al, 2010).…”

Section: Localisationmentioning

confidence: 99%

“…- Huggins and Andrulis (2008) suggested that LIMD1 may play a part in cell anchoring as a component of focal adhesions and in the cell cycle (especially during mitosis), based on the respective observations that LIMD1 colocalises with vinculin at focal adhesions and that phosphorylation of LIMD1 occurs during mitosis in HeLa cells.…”

Section: Functionmentioning

confidence: 99%

LIMD1 (LIM domains containing 1)

Wong¹,

Longmore²,

Sharp³

2012

Atlas of Genetics and Cytogenetics in Oncology and Haematology

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LIMD1‐AS1 suppressed non‐small cell lung cancer progression through stabilizing LIMD1 mRNA via hnRNP U

et al. 2020

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Background Non‐small cell lung cancer (NSCLC) occupies the majority of lung cancer cases and is notorious for the awful prognosis. LIM domains‐containing 1 (LIMD1) is suggested as a tumor suppressor in lung cancer, but its mechanism in NSCLC remains elusive. Present study aimed to uncover the mechanism of LIMD1 in NSCLC. Methods qRT‐PCR was performed to analyze the level of LIMD1. The functions of LIMD1 in NSCLC cells were evaluated by CCK‐8, EdU, and caspase‐3 activity assays. RIP and pull‐down assays were applied to determine the interaction of LIMD1 with heterogeneous nuclear ribonucleoprotein U (hnRNP U) and LIMD1‐AS1. Results LIMD1 was downregulated in NSCLC samples and cells. Functionally, LIMD1 hindered proliferation and drove apoptosis in NSCLC cells. Moreover, long noncoding RNA (lncRNA) LIMD1 antisense RNA 1 (LIMD1‐AS1) was downregulated in NSCLC samples and cell lines. LIMD1‐AS1 knockdown abrogated NSCLC cell growth in vitro and in vivo. Mechanistically, LIMD1‐AS1 stabilized LIMD1 mRNA through interacting with hnRNP U. Rescue experiments suggested that LIMD1‐AS1 repressed NSCLC progression through LIMD1. Conclusions LIMD1‐AS1 suppressed NSCLC progression through stabilizing LIMD1 mRNA via hnRNP U, providing new thoughts for the improvement of molecular‐targeted therapy for NSCLC.

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Cell cycle regulated phosphorylation of LIMD1 in cell lines and expression in human breast cancers

Cited by 34 publications

References 19 publications

Differential subcellular localisation of the tumour suppressor protein LIMD1 in breast cancer correlates with patient survival

Differential subcellular localisation of the tumour suppressor protein LIMD1 in breast cancer correlates with patient survival

LIMD1 (LIM domains containing 1)

LIMD1‐AS1 suppressed non‐small cell lung cancer progression through stabilizing LIMD1 mRNA via hnRNP U

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