KIBRA Modulates Directional Migration of Podocytes

Duning, Kerstin; Schurek, Eva-Maria; Schlüter, Marc A.; Bayer, Michael; Reinhardt, Hans-Christian; Schwab, Albrecht; Schaefer, Liliana; Benzing, Thomas; Schermer, Bernhard; Saleem, Moin A.; Huber, Tobias B.; Bachmann, S.; Kremerskothen, Joachim; Weide, Thomas; Pavenstädt, Hermann

doi:10.1681/asn.2007080916

Cited by 111 publications

(150 citation statements)

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“…This upstream regulator of Hippo pathway (40)(41)(42) controls the activity of the transcriptional coactivator YAP through its interaction with large-tumor suppressor kinase 1 (LATS1) and LATS2 kinases (42). Alongside these characterized functions in Hippo signaling, recent studies have revealed a role for KIBRA in cell migration and polarization (43)(44)(45). Overexpression of KIBRA can inhibit migration of MCF10A cells (44).…”

Section: Overexpression Of Kibra Rescues the Migration And Adhesionmentioning

confidence: 99%

Human phosphatase CDC14A is recruited to the cell leading edge to regulate cell migration and adhesion

Chen

Uddin

Voit

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Cell adhesion and migration are highly dynamic biological processes that play important roles in organ development and cancer metastasis. Their tight regulation by small GTPases and protein phosphorylation make interrogation of these key processes of great importance. We now show that the conserved dualspecificity phosphatase human cell-division cycle 14A (hCDC14A) associates with the actin cytoskeleton of human cells. To understand hCDC14A function at this location, we manipulated native loci to ablate hCDC14A phosphatase activity (hCDC14A PD ) in untransformed hTERT-RPE1 and colorectal cancer (HCT116) cell lines and expressed the phosphatase in HeLa FRT T-Rex cells. Ectopic expression of hCDC14A induced stress fiber formation, whereas stress fibers were diminished in hCDC14A PD cells. hCDC14A PD cells displayed faster cell migration and less adhesion than wild-type controls. hCDC14A colocalized with the hCDC14A substrate kidneyand brain-expressed protein (KIBRA) at the cell leading edge and overexpression of KIBRA was able to reverse the phenotypes of hCDC14A PD cells. Finally, we show that ablation of hCDC14A activity increased the aggressive nature of cells in an in vitro tumor formation assay. Consistently, hCDC14A is down-regulated in many tumor tissues and reduced hCDC14A expression is correlated with poorer survival of patients with cancer, to suggest that hCDC14A may directly contribute to the metastatic potential of tumors. Thus, we have uncovered an unanticipated role for hCDC14A in cell migration and adhesion that is clearly distinct from the mitotic and cytokinesis functions of Cdc14/Flp1 in budding and fission yeast.CDC14 | cell migration | cell adhesion | phosphatase

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Section: Overexpression Of Kibra Rescues the Migration And Adhesionmentioning

confidence: 99%

Human phosphatase CDC14A is recruited to the cell leading edge to regulate cell migration and adhesion

Chen

Uddin

Voit

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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“…Two studies have investigated KIBRA signaling in podocytes. The first, by Duning et al (14) in 2008, identified KIBRA's presence in podocytes of the glomerular tuft and in renal tubular cells. This study demonstrated that KIBRA interacts with the actin-bundling protein synaptopodin and the cell polarity protein PATJ.…”

Section: Glomerulusmentioning

confidence: 99%

Hippo signaling in the kidney: the good and the bad

Wong

Meliambro

Ray

et al. 2016

American Journal of Physiology-Renal Physiology

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The Hippo signaling pathway is an evolutionarily conserved kinase cascade, playing multiple roles in embryonic development that controls organ size, cell proliferation, and apoptosis. At the center of this network lie the Hippo kinase target and downstream pathway effector Yes-associated protein (YAP) and its paralog TAZ. In its phosphorylated form, cytoplasmic YAP is sequestered in an inactive state. When it is dephosphorylated, YAP, a potent oncogene, is activated and relocates to the nucleus to interact with a number of transcription factors and signaling regulators that promote cell growth, differentiation, and survival. The identification of YAP activation in human cancers has made it an attractive target for chemotherapeutic drug development. Little is known to date about the function of the Hippo pathway in the kidney, but that is rapidly changing. Recent studies have shed light on the role of Hippo-YAP signaling in glomerular and lower urinary tract embryonic development, maintenance of podocyte homeostasis, the integrity of the glomerular filtration barrier, regulation of renal tubular cyst growth, renal epithelial injury in diabetes, and renal fibrogenesis. This review summarizes the current knowledge of the Hippo-YAP signaling axis in the kidney under normal and disease conditions.

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“…KIBRA was originally identified as a memory performance-associated protein in humans (28 -32), and this function was recently confirmed in mice (33). The physiological function of KIBRA in non-neuronal cells is much less defined, although KIBRA has been shown to be involved in cell migration in podocytes (34) and NRK cells (35) and in epithelial cell polarity (36). KIBRA also interacts with the motor protein dynein light chain 1 to positively regulate cell growth in breast cancer cells (37).…”

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confidence: 99%