Lasp1 promotes malignant phenotype of non-small-cell lung cancer via inducing phosphorylation of FAK-AKT pathway

Zhang, Xiupeng; Liu, Yang; Fan, Chuifeng; Wang, Liang; Li, Ailin; Zhou, Haijing; Cai, Lin; Miao, Yuan; Li, Qingchang; Qiu, Xueshan; Wang, Enhua

doi:10.18632/oncotarget.20527

Cited by 33 publications

(33 citation statements)

References 42 publications

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“…Furthermore, the work by Duvall-Noelle et al showed association of LASP1 with UHRF1 and G9a in a CXCL12-dependent manner, assuming that LASP1, in addition, serves as a nuclear hub for the epigenetic machinery in breast cancer cells ( 19 ). Recently, this work was confirmed by data showing an enhanced Snail expression and decreased E-cadherin levels also in NSCLC after LASP1 overexpression ( 63 ).…”

Section: Functional Roles Of Lasp1 In Cancersupporting

confidence: 62%

New Frontiers for the Cytoskeletal Protein LASP1

Butt¹,

Raman

2018

Front. Oncol.

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In the recent two decades, LIM and SH3 protein 1 (LASP1) has been developed from a simple actin-binding structural protein to a tumor biomarker and subsequently to a complex, nuclear transcriptional regulator. Starting with a brief historical perspective, this review will mainly compare and contrast LASP1 and LASP2 from the angle of the newest data and importantly, examine their role in transcriptional regulation. We will summarize the current knowledge through pictorial models and tables including the roles of different microRNAs in the differential regulation of LASP1 levels and patient outcome rather than specify in detail all tumor entities. Finally, the novel functional roles of LASP1 in secretion of vesicles, expression of matrix metalloproteinases and transcriptional regulation as well as the activation of survival and proliferation pathways in different cancer types are described.

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Section: Functional Roles Of Lasp1 In Cancersupporting

confidence: 62%

New Frontiers for the Cytoskeletal Protein LASP1

Butt¹,

Raman

2018

Front. Oncol.

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“…Zhou R et al reported that COPS5 and LASP1 synergistically interacted to induce colorectal cancer progression by PI3K/AKT pathway [20]. In non-small cell lung cancer (NSCLC), LASP1 directly bound to FAK and enhanced the phosphorylation of FAK and AKT, thereby inducing cell proliferation and invasion [54]. Gao QZ et al found that LASP1 regulated nasopharyngeal carcinoma cell aggressiveness via LASP1/PTEN/PI3K/AKT axis [55].…”

Section: Discussionmentioning

confidence: 99%

ANLN-induced EZH2 upregulation promotes pancreatic cancer progression by mediating miR-218-5p/LASP1 signaling axis

Wang

Dai

Gong

et al. 2019

J Exp Clin Cancer Res

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Background: Pancreatic cancer is a highly lethal malignancy with poor prognosis. Anillin (ANLN), an actin binding protein, is upregulated and plays an important role in many malignant tumors. However, the precise role of ANLN in pancreatic cancer remains unclear. Methods: The expression of ANLN and its association with pancreatic cancer patient survival were analyzed using an online database and confirmed by immunohistochemistry. The ANLN protein expression in pancreatic cancer cell lines was detected by Western blot. Cell proliferation, colony formation and transwell assays in vitro and in vivo tumor growth were used to determine the role of ANLN in pancreatic cancer. Gene expression microarray analysis and a series of in vitro assays were used to elucidate the mechanisms of ANLN regulating pancreatic cancer progression.Results: We found that the ANLN expression was significantly upregulated in pancreatic cancer tissues and cell lines. The high expression of ANLN was associated with tumor size, tumor differentiation, TNM stage, lymph node metastasis, distant metastasis and poor prognosis in pancreatic cancer. ANLN downregulation significantly inhibited cell proliferation, colony formation, migration, invasion and tumorigenicity in nude mice. Meanwhile, we found that ANLN knockdown inhibited several cell-cell adhesion related genes, including the gene encoding LIM and SH3 protein 1 (LASP1). LASP1 upregulation partially reversed the tumor-suppressive effect of ANLN downregulation on pancreatic cancer cell progression. Moreover, we found that ANLN downregulation induced the expression of miR-218-5p which inhibited LASP1 expression through binding to its 3'UTR. We also found that ANLN-induced enhancer of zeste homolog 2 (EZH2) upregulation was involved in regulating miR-218-5p/LASP1 signaling axis. EZH2 upregulation or miR-218-5p downregulation partially reversed the tumor-suppressive effect of ANLN downregulation on pancreatic cancer cell progression. Conclusion: ANLN contributed to pancreatic cancer progression by regulating EZH2/miR-218-5p/LASP1 signaling axis. These findings suggest that ANLN may be a candidate therapeutic target in pancreatic cancer.

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“…Decreased pAKT1-S473 phosphorylation after LASP1 depletion has been observed before in several tumor cell lines, glioblastoma [21], gall bladder [22] and nasopharyngeal carcinoma [23], while LASP1 overexpression induces phosphorylation in colorectal cancer cells [24] and non-small cell lung cancer [25]. However, the underlying mechanisms are still controversial.…”

Section: Introductionmentioning

confidence: 87%

Phosphorylation-Dependent Differences in CXCR4-LASP1-AKT1 Interaction between Breast Cancer and Chronic Myeloid Leukemia

Butt

Stempfle

Lister

et al. 2020

Cells

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The serine/threonine protein kinase AKT1 is a downstream target of the chemokine receptor 4 (CXCR4), and both proteins play a central role in the modulation of diverse cellular processes, including proliferation and cell survival. While in chronic myeloid leukemia (CML) the CXCR4 is downregulated, thereby promoting the mobilization of progenitor cells into blood, the receptor is highly expressed in breast cancer cells, favoring the migratory capacity of these cells. Recently, the LIM and SH3 domain protein 1 (LASP1) has been described as a novel CXCR4 binding partner and as a promoter of the PI3K/AKT pathway. In this study, we uncovered a direct binding of LASP1, phosphorylated at S146, to both CXCR4 and AKT1, as shown by immunoprecipitation assays, pull-down experiments, and immunohistochemistry data. In contrast, phosphorylation of LASP1 at Y171 abrogated these interactions, suggesting that both LASP1 phospho-forms interact. Finally, findings demonstrating different phosphorylation patterns of LASP1 in breast cancer and chronic myeloid leukemia may have implications for CXCR4 function and tyrosine kinase inhibitor treatment.

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Lasp1 promotes malignant phenotype of non-small-cell lung cancer via inducing phosphorylation of FAK-AKT pathway

Cited by 33 publications

References 42 publications

New Frontiers for the Cytoskeletal Protein LASP1

New Frontiers for the Cytoskeletal Protein LASP1

ANLN-induced EZH2 upregulation promotes pancreatic cancer progression by mediating miR-218-5p/LASP1 signaling axis

Phosphorylation-Dependent Differences in CXCR4-LASP1-AKT1 Interaction between Breast Cancer and Chronic Myeloid Leukemia

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