Src-inducible association of CrkL with procaspase-8 promotes cell migration

Graf, Ryon P.; Barbero, Simone; Keller, N.; Chen, Lauren; Schlaepfer, David D.; Stupack, Dwayne G.

doi:10.4161/cam.25284

Cited by 13 publications

(7 citation statements)

References 27 publications

(72 reference statements)

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“…4), respectively, which was also consistent with our previous report that CRKL overexpression suppressed the in vitro migration and invasion potentials of Hca-P [23]. CRKL level was reported to enhance cell migration abilities either via mediating procaspase-8 recruitment to cell periphery and focal adhesions Src activation [37] or via forming a complex with Cbl cooperating with C3G [38]. Herein, the evidences from both CRKL overexpression [23] and knockdown [current work] experiments suggested the inverse correlation of CRKL with the in vitro migration and invasion capacities of Hca-P cells.…”

Section: Tablesupporting

confidence: 91%

CRKL knockdown promotes in vitro proliferation, migration and invasion, in vivo tumor malignancy and lymph node metastasis of murine hepatocarcinoma Hca-P cells

Meng

Sun

Guo

et al. 2015

Biomedicine & Pharmacotherapy

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Section: Tablesupporting

confidence: 91%

CRKL knockdown promotes in vitro proliferation, migration and invasion, in vivo tumor malignancy and lymph node metastasis of murine hepatocarcinoma Hca-P cells

Meng

Sun

Guo

et al. 2015

Biomedicine & Pharmacotherapy

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“…Previous reports have indicated that CrkL functions as an adaptor protein that links Src and C3G proteins (31,32). Increased activity of Src is a frequent occurrence in many types of human cancer, and there is growing evidence of a prominent role of Src in invasion and in other tumor progression-related events, such as the epithelial-mesenchymal transition and development of metastasis (33–35).…”

Section: Discussionmentioning

confidence: 99%

Crk-like adapter protein is overexpressed in cervical carcinoma, facilitates proliferation, invasion and chemoresistance, and regulates Src and Akt signaling

Zhang

et al. 2016

Oncology Letters

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Overexpression of Crk-like (CrkL) adapter protein has been implicated in a number of types of human cancer. However, its involvement in human cervical carcinoma remains unclear. The present study aimed to explore the clinical significance and biological characteristics of CrkL in human cervical carcinoma. CrkL protein expression was examined in tissue samples from 92 cases of cervical carcinoma using immunohistochemistry, and was found to be overexpressed in 48.9% (45/92 cases). CrkL was transfected into HeLa and CaSki cervical carcinoma cell lines and its effects on biological behavior were examined. CrkL overexpression was revealed to promote cell proliferation, invasion and chemoresistance. In addition, CrkL overexpression increased the level of Src and Akt phosphorylation. Treatment with the Src inhibitor dasatinib eliminated the effect of CrkL on cell invasion. In conclusion, the current results demonstrate that CrkL is an oncoprotein overexpressed in cervical carcinoma which contributes to malignant cell growth and chemoresistance. In addition, the findings indicate that CrkL promotes cervical cancer cell invasion through a Src-dependent pathway.

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“…One of the non-apoptotic functions of caspase 8 is to promote cell migration by interacting with pathways controlling focal adhesion turnover [ 56 ]. Association of caspase 8 with focal adhesion proteins is dependent on cell adhesion [ 57 ], suggesting that increasing the number of ligated integrins may direct caspase 8 to focal adhesions. Therefore, changes in the pattern of ligated integrins may redirect subcellular localization of caspase 8 resulting in the inability of activated death receptors to recruit a critical mass of procaspase to the developing DISC.…”

Section: Discussionmentioning

confidence: 99%

The fibronectin III-1 domain activates a PI3-Kinase/Akt signaling pathway leading to αvβ5 integrin activation and TRAIL resistance in human lung cancer cells

et al. 2016

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BackgroundFibronectin is a mechanically sensitive protein which is organized in the extracellular matrix as a network of interacting fibrils. The lung tumor stroma is enriched for fibronectin which is thought to contribute to metastasis and drug resistance. Fibronectin is an elastic, multi-modular protein made up of individually folded domains, some of which can stretch in response to increased mechanical tension. Very little is known about the relationship of fibronectin’s unfolded domains to lung cancer resistance to chemotherapy. In the present study, we evaluated the impact of unfolding the first Type III domain of fibronectin (FnIII-1c) on TNF-related apoptosis inducing ligand (TRAIL) resistance.MethodsNCI-H460 non-small cell lung cancer cells were treated with FnIII-1c then assessed for TRAIL-induced apoptosis. Subsequent analysis of FnIII-1c-mediated signaling pathways was also completed. Human non-small cell lung cancer tissue sections were assessed for the expression of vitronectin by immunohistochemistry.ResultsFnIII-1c inhibited TRAIL-induced activation of caspase 8 and subsequent apoptosis in NCI-H460 lung cancer cells. FnIII-1c treatment was associated with the activation of the phosphatidylinositol-3-kinase/alpha serine/threonine kinase (PI3K/Akt) pathway and the αvβ5 integrin receptor for vitronectin, both of which were required for TRAIL resistance. Immunohistochemical staining of sections from non-small cell lung cancers showed that vitronectin was localized around blood vessels and in the tumor-stroma interface.ConclusionsUnfolding of Type III domains within the fibronectin matrix may promote TRAIL resistance through the activation of a PI3K/Akt/αvβ5 signaling axis and point to a novel mechanism by which changes in secondary structure of fibronectin contribute to cancer cell resistance to apoptosis.

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Src-inducible association of CrkL with procaspase-8 promotes cell migration

Cited by 13 publications

References 27 publications

CRKL knockdown promotes in vitro proliferation, migration and invasion, in vivo tumor malignancy and lymph node metastasis of murine hepatocarcinoma Hca-P cells

CRKL knockdown promotes in vitro proliferation, migration and invasion, in vivo tumor malignancy and lymph node metastasis of murine hepatocarcinoma Hca-P cells

Crk-like adapter protein is overexpressed in cervical carcinoma, facilitates proliferation, invasion and chemoresistance, and regulates Src and Akt signaling

The fibronectin III-1 domain activates a PI3-Kinase/Akt signaling pathway leading to αvβ5 integrin activation and TRAIL resistance in human lung cancer cells

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