FER kinase promotes breast cancer metastasis by regulating α6- and β1-integrin-dependent cell adhesion and anoikis resistance

Ivanova, Iordanka A.; Vermeulen, Jeroen F.; Ercan, Cigdem; Houthuijzen, Julia M.; Saig, F. Al; Vlug, Eva J.; Wall, Elsken van der; Diest, Paul J. van; Vooijs, Marc; Derksen, Patrick W.B.

doi:10.1038/onc.2013.277

Cited by 60 publications

(80 citation statements)

References 54 publications

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“…Interesting studies have been published with promising results in targeting these integrins such as through the use of short hairpin RNAs or micro-RNAs (94). Targeting gene signaling pathways associated with these integrins or even specific kinases such as feline sarcoma-related kinase, which controls migration and metastasis of IBC cell lines by regulating CD49f-and CD29-integrin-dependent adhesion, is also an interesting approach (95).…”

Section: Integrinsmentioning

confidence: 99%

Implications of Different Cancer Stem Cell Phenotypes in Breast Cancer

Paula

Lopes

2017

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Section: Integrinsmentioning

confidence: 99%

Implications of Different Cancer Stem Cell Phenotypes in Breast Cancer

Paula

Lopes

2017

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“…Increased Fer expression in RCC cells has previously been demonstrated to be positively associated with tumor growth and progression in patients with RCC (6). A similar phenomenon has been reported in other malignancies, including breast and lung cancer (16,26). However, the association between stromal Fer expression, tumor malignancy and survival remains to be elucidated.…”

Section: Stromal Fer Expression -------------------------------------mentioning

confidence: 69%

“…Fer has been demonstrated to regulate cell proliferation, migration and adhesion, in fibroblasts and various types of immune cells (9,(11)(12)(13). Conversely, Fer is known to be associated with malignant aggressiveness in several types of cancer, including increased cell proliferation, invasion and metastasis (14)(15)(16).…”

Section: Introductionmentioning

confidence: 99%

Stromal expression of Fer suppresses tumor progression in renal cell carcinoma and is a predictor of survival

et al. 2016

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Abstract. Fps/Fes related (Fer) is a non-receptor tyrosine kinase that is expressed in fibroblasts, immune cells and endothelial cells. Fer serves an important pathological role in cell survival, angiogenesis and the immune system. However, the pathological role of Fer expression in the stromal cells surrounding renal cell carcinoma (RCC) has not been previously investigated. In the present study, immunohistochemical analysis of Fer was performed using the formalin-fixed tissue samples of 152 patients with RCC. The proliferative and apoptotic indices were used to represent the percentage of proliferation marker protein Ki-67-and cleaved caspase-3-positive cells, respectively. The microvessel density was defined as the number of cluster of differentiation (CD) 31-positively stained vessels/mm 2 . In addition, CD57 + and CD68 + cells were counted using semi-quantification of natural killer (NK) cells and macrophages. Fer expression in stromal cells was negatively associated with Fuhrman grade, pathological tumor stage and metastasis (P<0.001). Fer expression in stromal cells was negatively associated with CD68 + macrophage density, whereas it was positively associated with CD57 + NK cell density. Kaplan-Meier estimators indicated that decreased stromal Fer expression was a predictive marker of decreased cause-specific survival rate (P<0.001). Furthermore, low expression of Fer was identified as being an independent marker of decreased cause-specific survival using multivariate analysis (hazard ratio, 7.4; 95% confidence interval, 1.7-33.0; P<0.001). The results of the present study suggested that low Fer expression in stromal cells is associated with increased malignant aggressiveness and decreased survival in patients with RCC. CD57 + NK cell and CD68 + macrophage regulation in cancer-stromal tissue is considered to affect RCC pathology.

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“…Invasive cancer cells take advantage of these processes during cancer cell invasion and tumor metastasis (38). This study adds to a growing list of membrane shaping BAR proteins that have been implicated in cancer metastasis (14,15,19,22,39,40). Through stable silencing of Endo II in TNBC cell models, we provide evidence that Endo II promotes internalization of EGFR and downstream signaling to Erk and Akt pathways.…”

Section: Discussionmentioning

confidence: 83%

Endophilin A2 Promotes TNBC Cell Invasion and Tumor Metastasis

Baldassarre

Watt

Truesdell

et al. 2015

Molecular Cancer Research

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Triple-negative breast cancers (TNBCs) are highly aggressive cancers that lack targeted therapies. However, EGFR is frequently activated in a subset of TNBCs and represents a viable clinical target. Because the endocytic adaptor protein Endophilin A2 (SH3GL1/Endo II) has been implicated in EGFR internalization, we investigated Endo II expression and function in human TNBCs. Endo II expression was high in several TNBC cells compared with normal breast epithelial cells. Stable knockdown (KD) of Endo II was achieved in two TNBC cell lines, and although cell viability was unaffected, defects in receptor-mediated endocytosis were observed. EGFR signaling to Erk and Akt kinases was impaired in Endo II KD cells, and this correlated with reduced rates of EGFR internalization and cell motility. Endo II KD cells also displayed defects in three dimensional (3D) cell invasion, and this correlated with impaired extracellular matrix degradation and internalization of MT1-MMP. Endo II silencing also caused a significant reduction in TNBC tumor growth and lung metastasis in mammary orthotopic tumor xenograft assays. In human breast tumor specimens, Endo II expression was highest in TNBC tumors compared with other subtypes, and at the level of gene expression, high Endo II was associated with reduced relapse-free survival in patients with basal-like breast cancers. Together, these results identify a positive role for Endo II in TNBC tumor metastasis and a potential link with poor prognosis.Implications: Endophilin A2 and related adaptor proteins represent important signaling hubs to target in metastatic cancers. Mol Cancer Res; 13(6); 1044-55. Ó2015 AACR.

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FER kinase promotes breast cancer metastasis by regulating α6- and β1-integrin-dependent cell adhesion and anoikis resistance

Cited by 60 publications

References 54 publications

Implications of Different Cancer Stem Cell Phenotypes in Breast Cancer

Implications of Different Cancer Stem Cell Phenotypes in Breast Cancer

Stromal expression of Fer suppresses tumor progression in renal cell carcinoma and is a predictor of survival

Endophilin A2 Promotes TNBC Cell Invasion and Tumor Metastasis

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