An update on the LIM and SH3 domain protein 1 (LASP1): a versatile structural, signaling, and biomarker protein

Orth, Martin F.; Cazes, Alex; Butt, Elke; Grünewald, Thomas G.P.

doi:10.18632/oncotarget.3083

Cited by 72 publications

(111 citation statements)

References 107 publications

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“…LIM and SH3 domain protein (LASP1) a dynamic protein involved in cell structure, physiological processes and cell signaling, is significantly expressed in various malignancies and associated with tumor aggressiveness [40] and is reported to be an independent prognostic factor in patient’s survival for gastric cancer [41] and hepatocellular carcinoma [42]. We also found that LASP1 was associated with poor overall survival in our cohort.…”

Section: Discussionsupporting

confidence: 63%

Proteomic profiling of lung adenocarcinoma indicates heightened DNA repair, antioxidant mechanisms and identifies LASP1 as a potential negative predictor of survival

et al. 2016

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BackgroundLung cancer is the leading cause of cancer mortality in the United States. Non-small cell lung cancer accounts for 85% of all lung cancers for which adenocarcinoma is the most common histological type. Management of lung cancer is hindered by high false-positive rates due to difficulty resolving between benign and malignant tumors. Better molecular analysis comparing malignant and non-malignant tissues will provide important evidence of the underlying biology contributing to tumorigenesis.MethodsWe utilized a proteomics approach to analyze 38 malignant and non-malignant paired tissue samples obtained from current or former smokers with early stage (Stage IA/IB) lung adenocarcinoma. Statistical mixed effects modeling and orthogonal partial least squares discriminant analysis were used to identify key cancer-associated perturbations in the adenocarcinoma proteome. Identified proteins were subsequently assessed against clinicopathological variables.ResultsTop cancer-associated protein alterations were characterized by: (1) elevations in APEX1, HYOU1 and PDIA4, indicative of increased DNA repair machinery and heightened anti-oxidant defense mechanisms; (2) increased LRPPRC, STOML2, COPG1 and EPRS, suggesting altered tumor metabolism and inflammation; (3) reductions in SPTB, SPTA1 and ANK1 implying dysregulation of membrane integrity; and (4) decreased SLCA41 suggesting altered pH regulation. Increased protein levels of HYOU1, EPRS and LASP1 in NSCLC adenocarcinoma was independently validated by tissue microarray immunohistochemistry. Immunohistochemistry for HYOU1 and EPRS indicated AUCs of 0.952 and 0.841, respectively, for classifying tissue as malignant. Increased LASP1 correlated with poor overall survival (HR 3.66 per unit increase; CI 1.37–9.78; p = 0.01).ConclusionThese results reveal distinct proteomic changes associated with early stage lung adenocarcinoma that may be useful prognostic indicators and therapeutic targets.Electronic supplementary materialThe online version of this article (doi:10.1186/s12014-016-9132-y) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 63%

Proteomic profiling of lung adenocarcinoma indicates heightened DNA repair, antioxidant mechanisms and identifies LASP1 as a potential negative predictor of survival

et al. 2016

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“…As LASP1 is overexpressed in several cancer entities [14] it was tempting to speculate that the protein might also be involved in the development and progression of melanoma.…”

Section: Resultsmentioning

confidence: 99%

LASP1, a Newly Identified Melanocytic Protein with a Possible Role in Melanin Release, but Not in Melanoma Progression

et al. 2015

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The LIM and SH3 protein 1 (LASP1) is a focal adhesion protein. Its expression is increased in many malignant tumors. However, little is known about the physiological role of the protein. In the present study, we investigated the expression and function of LASP1 in normal skin, melanocytic nevi and malignant melanoma. In normal skin, a distinct LASP1 expression is visible only in the basal epidermal layer while in nevi LASP1 protein is detected in all melanocytes. Melanoma exhibit no increase in LASP1 mRNA compared to normal skin. In melanocytes, the protein is bound to dynamin and mainly localized at late melanosomes along the edges and at the tips of the cell. Knockdown of LASP1 results in increased melanin concentration in the cells. Collectively, we identified LASP1 as a hitherto unknown protein in melanocytes and as novel partner of dynamin in the physiological process of membrane constriction and melanosome vesicle release.

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“…11-13 LASP1 encodes a LIM motif at its N-terminus and an src homology 3 (SH3) domain at its C-terminus. In LASP1, SH3 domain functions in protein-protein interactions 28,29 and LASP1 acts as an actin-binding protein and overexpression of LASP1 enhances cancer cell proliferation and invasion. 13,28,30 Our present data showed that LASP1 is a putative candidate of these antitumor miRNA regulation, suggesting that LASP1 is a key molecule for cancer cell aggressiveness.…”

Section: Discussionmentioning

confidence: 99%

Regulation of metastasis-promoting LOXL2 gene expression by antitumor microRNAs in prostate cancer

et al. 2016

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Our recent studies of microRNA (miRNA) expression signatures of prostate cancer (PCa) showed that six miRNAs (specifically, miR-26a, miR-26b, miR-29a, miR-29b, miR-29c and miR-218) were markedly reduced in cancer tissues. Moreover, ectopic expression of these miRNAs suppressed PCa cell aggressiveness, indicating that these miRNAs acted in concert to regulate genes that promoted metastasis. Genome-wide gene expression analysis and in silico database analysis identified a total of 35 candidate genes that promoted metastasis and were targeted by these 6 miRNAs. Using luciferase reporter assays, we showed that the lysyl oxidase-like 2 (LOXL2) gene was directly controlled by these tumor-suppressive miRNAs in PCa cells. Overexpression of LOXL2 was confirmed in PCa tissues and knockdown of the LOXL2 gene markedly inhibited the migration and invasion of PCa cells. Aberrant expression of LOXL2 enhanced migration and invasion of PCa cells. Downregulation of antitumor miRNAs might disrupt the tightly controlled RNA networks found in normal cells. New insights into the novel molecular mechanisms of PCa pathogenesis was revealed by antitumor miRNA-regulated RNA networks.

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An update on the LIM and SH3 domain protein 1 (LASP1): a versatile structural, signaling, and biomarker protein

Cited by 72 publications

References 107 publications

Proteomic profiling of lung adenocarcinoma indicates heightened DNA repair, antioxidant mechanisms and identifies LASP1 as a potential negative predictor of survival

Proteomic profiling of lung adenocarcinoma indicates heightened DNA repair, antioxidant mechanisms and identifies LASP1 as a potential negative predictor of survival

LASP1, a Newly Identified Melanocytic Protein with a Possible Role in Melanin Release, but Not in Melanoma Progression

Regulation of metastasis-promoting LOXL2 gene expression by antitumor microRNAs in prostate cancer

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