Cell Adhesion Molecule L1 Disrupts E-Cadherin-Containing Adherens Junctions and Increases Scattering and Motility of MCF7 Breast Carcinoma Cells

Shtutman, Michael; Levina, Elina; Ohouo, Patrice; Baig, Mirza S.; Roninson, Igor B.

doi:10.1158/0008-5472.can-06-2106

Cited by 119 publications

(123 citation statements)

References 51 publications

(57 reference statements)

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“…L1CAM family members L1, CHL1, and NrCAM have been annotated roles in cancer progression and metastasis, and are involved in the regulation of proliferation and migration of diverse cancer types 5, 7, 11, 18, 19, 20, 23, 28…”

Section: Discussionmentioning

confidence: 99%

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Copy number variation, increased gene expression, and molecular mechanisms of neurofascin in lung cancer

Erdem

Arnoldussen

Skaug

et al. 2017

Molecular Carcinogenesis

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Metastasis and cell adhesion are key aspects of cancer progression. Neurofascin (NFASC) is a member of the immunoglobulin superfamily of adhesion molecules and, while studies on NFASC are inadequate, other members have been indicated pivotal roles in cancer progression and metastasis. This study aimed at increasing the knowledge on the involvement of adhesion molecules in lung cancer progression by studying the regulation and role of NFASC in non‐small cell lung cancer (NSCLC). Here, copy number variations in the NFASC gene were analyzed in tumor and non‐tumorous lung tissues of 204 NSCLC patients. Frequent gene amplifications (OR = 4.50, 95%CI: 2.27‐8.92, P ≤ 0.001) and increased expression of NFASC (P = 0.034) were identified in tumors of NSCLC patients. Furthermore, molecular mechanisms of NFASC in lung cancer progression were evaluated by investigating the effects of NFASC silencing on cell proliferation, viability, migration, and invasion using siRNA technology in four NSCLC cell lines. Silencing of NFASC did not affect cell proliferation or viability but rather decreased NSCLC cell migration (P ≤ 0.001) and led to morphological changes, rearrangements in the actin cytoskeleton and changes in F‐actin networks in migrating NSCLC cell lines. This study is the first to report frequent copy number gain and increased expression of NFASC in NSCLC. Moreover, these data suggest that NFASC is a novel regulator of NSCLC cell motility and support a role of NFASC in the regulation of NSCLC progression.

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Section: Discussionmentioning

confidence: 99%

“…L1 is present mainly at the invasive front and not the tumor mass of colon cancers and induces expression of metastasis‐associated genes in fibroblast cells 7, 175, 1819…”

Section: Introductionmentioning

confidence: 99%

Copy number variation, increased gene expression, and molecular mechanisms of neurofascin in lung cancer

Erdem

Arnoldussen

Skaug

et al. 2017

Molecular Carcinogenesis

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“…The cells were extracted at 37°C with 200 L of 0.5% Triton X-100, 2.5 mmol/L EGTA (ethylene glycol tetraacetic acid), 5 mmol/L MgCl 2 (magnesium chloride), and 50 mmol/L PIPES (1,4-piperazinediethanesulfonic acid), pH 6.2, for 2 minutes. 32,33 The Triton X-100-soluble fraction was collected and the plates were washed twice with the same buffer. The insoluble fraction was extracted with 200 L of the buffer with 1% SDS.…”

Section: Immunoblot Analysismentioning

confidence: 99%

Tenascin C Induces Epithelial-Mesenchymal Transition–Like Change Accompanied by SRC Activation and Focal Adhesion Kinase Phosphorylation in Human Breast Cancer Cells

Nagaharu

Zhang

Yoshida

et al. 2011

The American Journal of Pathology

119

110

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Tenascin C (TNC) is an extracellular matrix glycoprotein up-regulated in solid tumors. Higher TNC expression is shown in invading fronts of breast cancer, which correlates with poorer patient outcome. We examined whether TNC induces epithelial-mesenchymal transition (EMT) in breast cancer. Immunohistochemical analysis of invasive ductal carcinomas showed that TNC deposition was frequent in stroma with scattered cancer cells in peripheral margins of tumors. The addition of TNC to the medium of the MCF-7 breast cancer cells caused EMT-like change and delocalization of E-cadherin and ␤-catenin from cell-cell contact. Although amounts of E-cadherin and ␤-catenin were not changed after EMT in total lysates, they were increased in the Triton X-100-soluble fractions, indicating movement from the membrane into the cytosol. In wound healing assay, cells were scattered from wound edges and showed faster migration after TNC treatment. The EMT phenotype was correlated with SRC activation through phosphorylation at Y418 and phosphorylation of focal adhesion kinase ( Epithelial cells are polarized and tightly interconnected by cellular junctions, whereas mesenchymal cells never form stable intercellular contacts in adult tissues. Epithelial-mesenchymal transition (EMT) is a process whereby polarized epithelial cells are converted into mesenchymal cells during embryogenesis and in diseased tissues. 1-4 EMT events also take place during tumor progression in association with invasion and metastasis, when carcinoma cells stably or transiently lose their epithelial polarity and intercellular connections, allowing them to escape the surrounding epithelium and acquire higher locomotive behavior like mesenchymal cells. 2,[5][6][7][8] Many recent studies have demonstrated that EMT is controlled by complex signaling pathways initiated from tyrosine-receptor kinases, transforming growth factor-␤ (TGF-␤) receptors, Wnt pathways, Notch pathways, and integrins, which are triggered by various extracellular signals. 2,4,9 The activated pathways, including RAS/ mitogen-activated protein kinase, phosphoinositol 3 kinase, SRC, and focal adhesion kinase (FAK), also induce cytoskeletal reorganization, causing dissociation of E-cadherin from the membrane, loss of epithelial morphology, and increased cell motility. 2,4,9,10 Expression of transcriptional regulators such as SNAI1/2 and TWIST, followed by transcriptional switching from epithelial markers to mesenchymal ones, also has been reported. 2,11,12

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“…Cells were contained CO 2 -independent medium in a temperature-controlled box stabilized at 37 1C. Images were collected every 3 min for 72 h using Leica ASMDW software as described previously (Shtutman et al, 2006).…”

Section: Western Blot Analysismentioning

confidence: 99%

Mechanism of G1-like arrest by low concentrations of paclitaxel: next cell cycle p53-dependent arrest with sub G1 DNA content mediated by prolonged mitosis

Demidenko

Kalurupalle²,

Hanko³

et al. 2008

Oncogene

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Paclitaxel (PTX) and other microtubule inhibitors cause mitotic arrest. However, low concentrations of PTX (low PTX) paradoxically cause G1 arrest (without mitotic arrest). Here, we demonstrated that unexpectedly, low PTX did not cause G1 arrest in the first cell cycle and did not prevent cells from passing through S phase and entering mitosis. Mitosis was prolonged but cells still divided, producing either two or three cells (tripolar mitosis), thus explaining a sub G1 peak caused by low PTX. Importantly, sub G1 cells were viable and nonapoptotic. Some cells fused back and then progressed to mitosis, frequently producing three cells again before becoming arrested in the next cell-cycle interphase. Thus, low PTX caused postmitotic arrest in second and even the third cell cycles. By increasing concentration of PTX, tripolar mitosis was transformed to mitotic slippage, thus eliminating a sub G1 peak. Time-lapse microscopy revealed that prolonged mitosis ensured a p53-dependent postmitotic arrest. We conclude that PTX directly affects cells only in mitosis and the duration of mitosis determines cell fate, including p53-dependent G1-like arrest.

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Cell Adhesion Molecule L1 Disrupts E-Cadherin-Containing Adherens Junctions and Increases Scattering and Motility of MCF7 Breast Carcinoma Cells

Cited by 119 publications

References 51 publications

Copy number variation, increased gene expression, and molecular mechanisms of neurofascin in lung cancer

Copy number variation, increased gene expression, and molecular mechanisms of neurofascin in lung cancer

Tenascin C Induces Epithelial-Mesenchymal Transition–Like Change Accompanied by SRC Activation and Focal Adhesion Kinase Phosphorylation in Human Breast Cancer Cells

Mechanism of G1-like arrest by low concentrations of paclitaxel: next cell cycle p53-dependent arrest with sub G1 DNA content mediated by prolonged mitosis

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