Untitled

Wong, Nanette C.; Mueller, Barbara M.; Barbas, Carlos F.; Ruminski, Pete; Quaranta, Vito; Lin, Emme C.K.; Smith, Jeffrey W.

doi:10.1023/a:1006512018609

Cited by 111 publications

(34 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Previous studies have demonstrated that MDA-MB-231 cells attach equally well on several ECM proteins, such as type I collagen, ®bronectin, laminin-1 and vitronectin (Lichtner et al, 1998;Lundstrom et al, 1998;van der Pluijm et al, 1997;Wong et al, 1998), and we found the same here. Also of note, no di erences in cell survival were observed when MDA-MB-231 cells were plated on di erent matrix substrates or on the non-integrin ligand polylysine for extended periods of time in the absence of any drug treatment (not shown).…”

Section: Resultssupporting

confidence: 88%

Integrin signaling inhibits paclitaxel-induced apoptosis in breast cancer cells

2001

View full text Add to dashboard Cite

Inherent or acquired drug resistance is one of the major problems in chemotherapy. The mechanisms by which cancer cells survive and escape the cytotoxic e ects of chemotherapeutic agents are essentially unknown. In the present study, we demonstrate that in the MDA-MB-231 and MDA-MB-435 breast cancer cells, ligation of b1 integrins by their extracellular matrix ligands inhibits signi®cantly apoptosis induced by paclitaxel and vincristine, two microtubule-directed chemotherapeutic agents that are widely used in the therapy of breast cancer. We show that b1 integrin signaling inhibits drug-induced apoptosis by inhibiting the release of cytochrome c from the mitochondria in response to drug treatment. Further, integrin-mediated protection from drug-induced apoptosis and inhibition of cytochrome c release are dependent on the activation of the PI 3-kinase/Akt pathway. Our results identify b1 integrin signaling as an important survival pathway in drug-induced apoptosis in breast cancer cells and suggest that activation of this pathway may contribute to the generation of drug resistance. Oncogene (2001) 20, 4995 ± 5004.

show abstract

Section: Resultssupporting

confidence: 88%

Integrin signaling inhibits paclitaxel-induced apoptosis in breast cancer cells

2001

View full text Add to dashboard Cite

show abstract

“…The former use the laminin receptor ␣ 6 ␤ 1 , whereas the latter primarily use the vitronectin receptor ␣ v ␤ 3 . This result extends previous results demonstrating the avid attachment of breast cells to vitronectin substrates (44,65). Breast cells have a large variety of integrin dimers on their surfaces for binding to matrix components (43), but primarily utilize ␣ v ␤ 1 , ␣ v ␤ 3 , and ␣ v ␤ 5 for vitronectin (66).…”

Section: Discussionsupporting

confidence: 87%

The Proliferative and Migratory Activities of Breast Cancer Cells Can Be Differentially Regulated by Heparan Sulfates

Nurcombe¹,

Smart²,

Chipperfield³

et al. 2000

Journal of Biological Chemistry

View full text Add to dashboard Cite

“…6b). This is consistent with the report that the expression of ␤3 in MCF-7 cells is very low (40). Our results suggest that ␣6␤4 integrin plays a major role in NRG signaling in MCF-7 cells.…”

Section: Nrg1 Induces Co-precipitation Of Integrins and Erbb3 Whereasupporting

confidence: 94%

Direct Binding of the EGF-like Domain of Neuregulin-1 to Integrins (αvβ3 and α6β4) Is Involved in Neuregulin-1/ErbB Signaling

Ieguchi

Fujita

et al. 2010

Journal of Biological Chemistry

View full text Add to dashboard Cite

Integrin-growth factor receptor cross-talk plays a role in growth factor signaling, but the specifics are unclear. In a current model, integrins and growth factor receptors independently bind to their ligands (extracellular matrix and growth factors, respectively). We discovered that neuregulin-1 (NRG1), either as an isolated EGF-like domain or as a native multi-domain form, binds to integrins ␣v␤3 (with a K D of 1.36 ؋ 10 ؊7 M) and ␣6␤4. Docking simulation predicted that three Lys residues at positions 180, 184, and 186 of the EGF-like domain are involved in integrin binding. Mutating these residues to Glu individually or in combination markedly suppressed integrin binding and ErbB3 phosphorylation. Mutating all three Lys residues to Glu (the 3KE mutation) did not affect the ability of NRG1 to bind to ErbB3 but markedly reduced the ability of NRG1 to induce ErbB3 phosphorylation and AKT and Erk1/2 activation in MCF-7 and T47D human breast cancer cells. This suggests that direct integrin binding to NRG1 is critical for NRG1/ErbB signaling. Notably, stimulation of cells with WT NRG1 induced co-precipitation of ErbB3 with ␣6␤4 and with ␣v␤3 to a much lower extent. This suggests that WT NRG1 induces integrin-NRG1-ErbB3 ternary complex formation. In contrast, the 3KE mutant was much less effective in inducing ternary complex formation than WT NRG1, suggesting that this process depends on the ability of NRG1 to bind to integrins. These results suggest that direct NRG1-integrin interaction mediates integrin-ErbB cross-talk and that ␣6␤4 plays a major role in NRG-ErbB signaling in these cancer cells.The neuregulins (NRGs) 2 are a family of four structurally related proteins that are part of the EGF family of proteins (NRG1-4) (1-4). Transmembrane NRGs typically function as precursor molecules that are cleaved by metalloproteases. This results in the release of the extracellular domain that may subsequently bind to nearby receptors (autocrine/paracrine action). NRGs contain an epidermal growth factor (EGF)-like motif that binds and activates receptor-tyrosine kinases in the EGF receptor (ErbBs) family. Neuregulin-1 (NRG1) binds to ErbB3 and ErbB4. NRG1 has 11 isoforms (5). NRG1 plays essential roles in the nervous system, heart, and breast. NRG1 signaling is involved in the development and functions of several other organ systems and human diseases, including schizophrenia (6), coronary heart diseases (7), and cancer (8). Targeted deletion of ErbB2, ErbB3, ErbB4, or NRG1 in mice leads to developmental abnormalities that are severe in the nervous system and lethal in the cardiovascular system (9 -11). In cancer the interaction between ErbB receptors and ligands such as NRGs plays an important role in tumor growth. The EGF-like motif of NRGs is essential and sufficient for receptor binding and activation as well as promoting tumorigenesis (12). The presence of the autocrine loop is one of the causes that induces aberrant ErbB receptor activation and has been correlated with cancer development and progression. Disrupting...

show abstract

Untitled

Cited by 111 publications

References 51 publications

Integrin signaling inhibits paclitaxel-induced apoptosis in breast cancer cells

Integrin signaling inhibits paclitaxel-induced apoptosis in breast cancer cells

The Proliferative and Migratory Activities of Breast Cancer Cells Can Be Differentially Regulated by Heparan Sulfates

Direct Binding of the EGF-like Domain of Neuregulin-1 to Integrins (αvβ3 and α6β4) Is Involved in Neuregulin-1/ErbB Signaling

Contact Info

Product

Resources

About