An Intracellular Signal Pathway That Regulates Cancer Cell Adhesion in Response to Extracellular Forces

Basson, Marc D.

doi:10.1158/0008-5472.can-07-2992

Cited by 48 publications

(52 citation statements)

References 20 publications

(20 reference statements)

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“…Although we did not investigate the involvement of FAK in ICAM-3-induced cell migration and invasion in this study, increase of radiation resistance induced by ICAM-3 was dependent on FAK activation (25). Many investigators have reported that interaction of FAK with Akt have various roles in cellular adhesion, cell survival and drug resistance and radio-resistance (41)(42)(43)(44). Therefore, we postulated that FAK could be one of the major components in ICAM-3-induced signaling.…”

Section: Discussionmentioning

confidence: 76%

ICAM-3 enhances the migratory and invasive potential of human non-small cell lung cancer cells by inducing MMP-2 and MMP-9 via Akt and CREB

Park

et al. 2009

Int J Oncol

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Abstract.We have previously reported that intercellular adhesion molecule-3 (ICAM-3) is associated with an increase of cellular radio-resistance and cancer cell proliferation. In this study, we hypothesized that ICAM-3 has an additional effect on cancer cell migration and invasion because molecules induced by ICAM-3 are known as regulators of cell migration and invasion. To examine this hypothesis, we used NCI-H1299 non-small cell lung cancer (NSCLC) cell line (p53 and PTEN null cell) and constructed an ICAM-3-over-expressing stable transfectant, which exhibited increased cell migration and invasion. The increased migration and invasion resulted from up-regulation of expression and activities of MMP-2 and MMP-9. ICAM-3 also increased Akt phosphorylation, which caused an increase in cellular migration/invasion and MMP activities. Activity of several transcriptional factors located downstream in the Akt pathway was also tested, and constitutive activation of adenosine 3', 5'-monophosphate response element-binding protein (CREB) by ICAM-3 was detected. Blockage of the Akt pathway attenuated CREB activation, and a decrease in CREB expression reduced cellular migration/invasion and activity of MMPs. This result indicates that CREB functions in the signaling pathway between Akt and MMP. We also showed ICAM-3-induced cell migration and invasion in NCI-H460 NSCLC cells (wild-type p53 and PTEN cell) through the same signaling pathway. Taken together, our findings suggest that ICAM-3 stimulates cancer cell migration/ invasion via ICAM-3/Akt/CREB/MMP pathway regardless of p53 and PTEN status, and this reflects the possibility that ICAM-3 could be considered as a candidate for anti-cancer drug development and as a cancer diagnostic marker.

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Section: Discussionmentioning

confidence: 76%

ICAM-3 enhances the migratory and invasive potential of human non-small cell lung cancer cells by inducing MMP-2 and MMP-9 via Akt and CREB

Park

et al. 2009

Int J Oncol

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“…They are rarely mutated in human tumors but are overexpressed or activated in a variety of tumors, including colon, breast, pancreatic, bladder, head and neck, ovarian, and brain (Summy and Gallick, 2003). Although Src is a proto-oncogene, its association with FAK (another nonreceptor tyrosine kinase) is critical for the formation of metastases (Basson, 2008). Therefore, Src is an emerging therapeutic target to prevent metastases from occurring (Sawyer, 2004;Rucci et al, 2008).…”

Section: When Normal Mefs and Ymentioning

confidence: 99%

Quantification of Focal Adhesion Kinase Activation Loop Phosphorylation as a Biomarker of Src Activity

Ciccimaro

Hanks²,

Blair

2008

Mol Pharmacol

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A recently developed stable isotope dilution liquid chromatography-multiple reaction/mass spectrometry method to quantify focal adhesion kinase (FAK) -benzodioxol-4-yl)-7-[2-(4-methylpiperazin-1-yl)ethoxy]-5-(tetrahydro-2H-pyran-4-yloxy)quinazolin-4-amine (AZD0530). Phosphorylation of FAK at Tyr 576 /Tyr 577 was inhibited by AZD0530 in a dose-dependent manner both in cell culture and in vitro. However, there was a substantial difference in the ability of AZD0530 to inhibit Src that was constitutively activated in a cellular context (IC 50 ϭ 2.12 M) compared with the isolated enzyme (IC 50 ϭ 0.14 M). When normal MEFs and Y529 FSrc-expressing MEFs were treated with pervanadate (a global phosphatase inhibitor), pTyr 576 /pTyr 577 -FAK accounted for almost 60% of the total FAK present in the cells. This suggests that activation loop phosphorylation is regulated by tyrosine phosphatases. These results confirm that FAK phosphorylation is a useful biomarker of Src inhibition in vivo. The accuracy and specificity of stable isotope dilution liquid chromatography-mass spectrometry methodology offers significant advantages over current immunochemical approaches for monitoring Src activity.

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“…This is achieved by inhibition (via phosphorylation) of caspase-9 and Apaf-1 as well as other proapoptotic proteins such as BAD and its downstream target BAX (36). Active Akt-1 commonly leads to cell proliferation and plays a role as an oncogene in tumorigenic processes (6,52).…”

mentioning

confidence: 99%

Simian Virus 40 Infection Triggers a Balanced Network That Includes Apoptotic, Survival, and Stress Pathways

Butin‐Israeli¹,

Drayman²,

Oppenheim³

2010

J Virol

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The infection process by simian virus 40 (SV40) and entry of its genome into nondividing cells are only partly understood. Infection begins by binding to GM1 receptors at the cell surface, cellular entry via caveolar invaginations, and trafficking to the endoplasmic reticulum, where the virus disassembles. To gain a deeper insight into the contribution of host functions to this process, we studied cellular signaling elicited by the infecting virus. Signaling proteins were detected by Western blotting and immunofluorescence staining. The study was assisted by a preliminary proteomic screen. The contribution of signaling proteins to the infection process was evaluated using specific inhibitors. We found that CV-1 cells respond to SV40 infection by activating poly(ADP-ribose) polymerase 1 (PARP-1)-mediated apoptotic signaling, which is arrested by the Akt-1 survival pathway and stress response. A single key regulator orchestrating the three pathways is phospholipase C-gamma (PLC␥). The counteracting apoptotic and survival pathways are robustly balanced as the infected cells neither undergo apoptosis nor proliferate. Surprisingly, we have found that the apoptotic pathway, including activation of PARP-1 and caspases, is absolutely required for the infection to proceed. Thus, SV40 hijacks the host defense to promote its infection. Activities of PLC␥ and Akt-1 are also required, and their inhibition abrogates the infection. Notably, this signaling network is activated hours before T antigen is expressed. Experiments with recombinant empty capsids, devoid of DNA, indicated that the major capsid protein VP1 alone triggers this early signaling network. The emerging robust signaling network reflects a delicate evolutionary balance between attack and defense in the host-virus relationship.

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An Intracellular Signal Pathway That Regulates Cancer Cell Adhesion in Response to Extracellular Forces

Cited by 48 publications

References 20 publications

ICAM-3 enhances the migratory and invasive potential of human non-small cell lung cancer cells by inducing MMP-2 and MMP-9 via Akt and CREB

ICAM-3 enhances the migratory and invasive potential of human non-small cell lung cancer cells by inducing MMP-2 and MMP-9 via Akt and CREB

Quantification of Focal Adhesion Kinase Activation Loop Phosphorylation as a Biomarker of Src Activity

Simian Virus 40 Infection Triggers a Balanced Network That Includes Apoptotic, Survival, and Stress Pathways

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