Novel focal adhesion protein kindlin‐2 promotes the invasion of gastric cancer cells through phosphorylation of integrin β1 and β3

Shen, Zhanlong; Ye, Yingjiang; Kauttu, Tuuli; Seppänen, Hanna; Vainionpää, Sanna; Wang, Shan; Mustonen, Harri; Puolakkainen, Pauli

doi:10.1002/jso.23353

Cited by 43 publications

(34 citation statements)

References 25 publications

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“…Kindlin-2 is a member of the kindlin family of focal adhesion proteins, and is involved in integrin signaling and linkage of the actin cytoskeleton to the extracellular matrix. Although few studies report on kindlin-2, it has been found to be up-regulated in breast and gastric cancer cell lines [29, 30], but down-regulated in leiomyosarcomas [31] and mesenchymal cancer cells [32]. Targeting kindlin-2 may improve drug efficacy and reduce the dose of drug required to treat prostate cancer [33].…”

Section: Discussionmentioning

confidence: 99%

A three-protein signature and clinical outcome in esophageal squamous cell carcinoma

et al. 2014

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Current staging is inadequate to precisely predict clinical outcome of esophageal squamous cell carcinoma (ESCC) and determine treatment choices, which vary from operation alone to intensive multimodal regimens. The purpose of this study is to investigate the prognostic values of an immunohistochemistry-based three-protein signature model in patients with ESCC. We determined the protein expression of Annexin II, cofilin 1, ezrin, fascin, kindlin-2, moesin, MTSS1, myosin-9, profilin-1, Rac1, radixin, ROCK2, talin, tensin and villin 1 in a test cohort including 110 formalin-fixed, paraffin-embedded esophageal curative resection specimens by tissue microarrays (TMAs). A three-protein signature elicited from the protein cluster, Annexin II, kindlin-2, and myosin-9, was validated by TMAs on an independent cohort of 147 specimens. The expression of three-protein signature was highly predictive of ESCC overall survival (OS) and disease-free survival (DFS) in both generation and validation datasets. Regression analysis shows that this three-protein signature is an independent predictor for OS and DFS. Furthermore, the predictive ability of these 3 biomarkers in combination is more robust than that of each individual biomarker. This study demonstrates a clinically applicable prognostic model that accurately predicts ESCC patient survival and/or tumor recurrence, and thus could serve as a complement to current risk stratification approaches.

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Section: Discussionmentioning

confidence: 99%

A three-protein signature and clinical outcome in esophageal squamous cell carcinoma

et al. 2014

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“…Interestingly, in esophageal SCC, kindlin-2 itself might be a target for miR-200b, resulting in decreased kindlin-2 levels and tumor cell invasion . In addition to regulation of EMT and invasion, kindlin-2 has been shown to promote cell survival through stimulation of Hedgehog signaling by inducing the expression of Loss of expression increases cell invasion EMMPRIN regulates kindlin-3 and β1 integrin expression Delyon et al, 2015 Gli1 and anti-apoptotic Bcl2 proteins (Gao et al, 2013;Gong et al, 2010;Shen et al, 2013). Kindlin-2 has also suggested to enhance genome instability, a hallmark of cancer formation, although it is not clear how this is achieved at the molecular level (Zhao et al, 2013).…”

Section: Kindlin-2 Is Involved In Multiple Diseasesmentioning

confidence: 99%

The kindlin family: functions, signaling properties and implications for human disease

Rognoni

Ruppert

Fässler

2016

Journal of Cell Science

200

186

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The kindlin (or fermitin) family of proteins comprises three members (kindlin-1,-2 and -3) of evolutionarily conserved focal adhesion (FA) proteins, whose best-known task is to increase integrin affinity for a ligand (also referred as integrin activation) through binding of β-integrin tails. The consequence of kindlin-mediated integrin activation and integrin-ligand binding is cell adhesion, spreading and migration, assembly of the extracellular matrix (ECM), cell survival, proliferation and differentiation.

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“…Kindlin-2 expression has been found to be dysregulated in several cancer types: prostate 74-77 breast 64, 78-80 , lung 65, 81 , colorectal cancer 82 , pancreas 83, 84 ovarian 85, 86 , esophageal squamous cell carcinoma 87-89 , liver 90 , brain 91 , gastric cancer 92, 93 , bladder 94 , and acute myeloid leukemia 95 . Given the association of kindlin-2 with several cancers of different origins, one can predict an important role that kindlin-2 may play in cancer pathogenesis.…”

Section: Association Of Kindlins With Cancermentioning

confidence: 99%

Of Kindlins and Cancer

Plow

Das

Białkowska

et al. 2016

Discoveries (Craiova)

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Kindlins are 4.1-ezrin-ridixin-moesin (FERM) domain containing proteins. There are three kindlins in mammals, which share high sequence identity. Kindlin-1 is expressed primarily in epithelial cells, kindlin-2 is widely distributed and is particularly abundant in adherent cells, and kindlin-3 is expressed primarily in hematopoietic cells. These distributions are not exclusive; some cells express multiple kindlins, and transformed cells often exhibit aberrant expression, both in the isoforms and the levels of kindlins. Great interest in the kindlins has emerged from the recognition that they play major roles in controlling integrin function. In vitro studies, in vivo studies of mice deficient in kindlins, and studies of patients with genetic deficiencies of kindlins have clearly established that they regulate the capacity of integrins to mediate their functions. Kindlins are adaptor proteins; their function emanate from their interaction with binding partners, including the cytoplasmic tails of integrins and components of the actin cytoskeleton. The purpose of this review is to provide a brief overview of kindlin structure and function, a consideration of their binding partners, and then to focus on the relationship of each kindlin family member with cancer. In view of many correlations of kindlin expression levels and neoplasia and the known association of integrins with tumor progression and metastasis, we consider whether regulation of kindlins or their function would be attractive targets for treatment of cancer.

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Novel focal adhesion protein kindlin‐2 promotes the invasion of gastric cancer cells through phosphorylation of integrin β1 and β3

Abstract: Kindlin-2 might promote the invasion of gastric cancer cells through enhancing proliferation and adhesion by the phosphorylation of integrin β1 and β3.

Cited by 43 publications

References 25 publications

A three-protein signature and clinical outcome in esophageal squamous cell carcinoma

A three-protein signature and clinical outcome in esophageal squamous cell carcinoma

The kindlin family: functions, signaling properties and implications for human disease

Of Kindlins and Cancer

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