The Fer Tyrosine Kinase Is Important for Platelet-derived Growth Factor-BB-induced Signal Transducer and Activator of Transcription 3 (STAT3) Protein Phosphorylation, Colony Formation in Soft Agar, and Tumor Growth in Vivo

Lennartsson, Johan; Ma, Haisha; Wardega, Piotr; Pelka, Karin; Engström, Ulla; Hellberg, Carina; Heldin, Carl‐Henrik

doi:10.1074/jbc.m113.476424

Cited by 29 publications

(22 citation statements)

References 34 publications

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“…For example, the requirement of Fer for the deregulated proliferation of cancer cells in vitro is most profoundly manifested when the cells are grown in agarose under nonanchoring conditions accompanied by restricted nutrient and oxygen availability (51). Furthermore, shRNA knockdown studies carried out with mouse xenografts models showed that Fer plays an important role during the initiation of primary tumors (51) and is essential for the development of secondary metastases (26,27). This might reflect, at least in part, a required contribution of Fer to the initiation and early stages of tumor formation, during which the nutrient and oxygen supplying vasculature has not yet been established.…”

Section: Discussionmentioning

confidence: 99%

Oncogenic Properties of a Spermatogenic Meiotic Variant of Fer Kinase Expressed in Somatic Cells

et al. 2014

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The kinase Fer and its spermatogenic meiotic variant, FerT, are coexpressed in normal testes and cancerous tumors, but whether they exert related roles in spermatogenic or malignant cells has not been known. Here, we show that Fer and FerT reside in the mitochondria of spermatogenic cells and are harnessed to the reprogrammed mitochondria of colon carcinoma cells. Both kinases bound complex I of the mitochondrial electron transport chain (ETC) in spermatogenic and in colon carcinoma cells, and silencing of either Fer or FerT was sufficient to impair the activity of this complex. Directed mitochondrial accumulation of FerT in nonmalignant NIH3T3 cells increased their ETC complex I activity, ATP production, and survival, contingent upon stress conditions caused by nutrient and oxygen deprivation. Strikingly, directed mitochondrial accumulation of FerT endowed nonmalignant cells with tumor-forming ability. Thus, recruitment of a meiotic mitochondrial component to cancer cell mitochondria highlights a pivotal role for reprogrammed mitochondria in tumorigenesis. Cancer Res; 74(22);

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Section: Discussionmentioning

confidence: 99%

Oncogenic Properties of a Spermatogenic Meiotic Variant of Fer Kinase Expressed in Somatic Cells

et al. 2014

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“…Beads were washed three times with ice-cold lysis buffer, and attached proteins were eluted by boiling for 5 min in reducing SDS sample buffer and then separated by SDS-PAGE. Immunoblotting was performed as described previously (13). For co-immunoprecipitation, starved cells were stimulated with 20 ng/ml PDGF-BB for the indicated periods of time and lysed in 1% Triton X-100, 20 mM Tris (pH 7.5), 150 mM NaCl, 1 mM Pefabloc, and 1 mM sodium orthovanadate and then subjected to immunoprecipitation followed by immunoblotting as described above.…”

Section: Methodsmentioning

confidence: 99%

The Ubiquitin Ligases c-Cbl and Cbl-b Negatively Regulate Platelet-derived Growth Factor (PDGF) BB-induced Chemotaxis by Affecting PDGF Receptor β (PDGFRβ) Internalization and Signaling

Rorsman

Tsioumpekou

Heldin

et al. 2016

Journal of Biological Chemistry

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“…Fer functions in regulating cell-cell adhesion, migration and proliferation. [19][20][21][22] Upregulation of Fer has been implicated in tumor progression in some human cancers. [23][24][25][26][27] Although these lines of evidence suggest that Fer has a crucial role in controlling malignant progression, the molecular mechanism of Fer activation and its precise functions remain unknown.…”

Section: Introductionmentioning

confidence: 99%

Fer tyrosine kinase oligomer mediates and amplifies Src-induced tumor progression

et al. 2015

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c-Src is upregulated in various human cancers, suggesting its role in malignant progression. However, the molecular circuits of c-Src oncogenic signaling remain elusive. Here we show that Fer tyrosine kinase oligomer mediates and amplifies Src-induced tumor progression. Previously, we showed that transformation of fibroblasts is promoted by the relocation of c-Src to non-raft membranes. In this study, we identified Fer and ezrin as non-raft c-Src targets. c-Src directly activated Fer by initiating its autophosphorylation, which was further amplified by Fer oligomerization. Fer interacted with active c-Src at focal adhesion membranes and activated Fer-phosphorylated ezrin to induce cell transformation. Fer was also crucial for cell transformation induced by v-Src or epidermal growth-factor receptor activation. Furthermore, Fer activation was required for tumorigenesis and invasiveness in some cancer cells in which c-Src is upregulated. We propose that the Src-Fer axis represents a new therapeutic target for treatment of a subset of human cancers.

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The Fer Tyrosine Kinase Is Important for Platelet-derived Growth Factor-BB-induced Signal Transducer and Activator of Transcription 3 (STAT3) Protein Phosphorylation, Colony Formation in Soft Agar, and Tumor Growth in Vivo

Cited by 29 publications

References 34 publications

Oncogenic Properties of a Spermatogenic Meiotic Variant of Fer Kinase Expressed in Somatic Cells

Oncogenic Properties of a Spermatogenic Meiotic Variant of Fer Kinase Expressed in Somatic Cells

The Ubiquitin Ligases c-Cbl and Cbl-b Negatively Regulate Platelet-derived Growth Factor (PDGF) BB-induced Chemotaxis by Affecting PDGF Receptor β (PDGFRβ) Internalization and Signaling

Fer tyrosine kinase oligomer mediates and amplifies Src-induced tumor progression

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