The Lipid Kinase PI4KIIIβ Is Highly Expressed in Breast Tumors and Activates Akt in Cooperation with Rab11a

Morrow, Anne A.; Alipour, Mohsen; Bridges, Dave; Yao, Zemin; Saltiel, Alan R.; Lee, Jonathan M.

doi:10.1158/1541-7786.mcr-13-0604

Cited by 36 publications

(45 citation statements)

References 65 publications

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“…In summary, we have identified an import role for PI4KIIIβ in cell shape, migration and adhesion. PI4KIIIΒ is likely to be a human oncogene (Waugh, 2012;Morrow et al, 2014) and we propose that its role in cancer is related to its regulation of these processes. In the further it will be important to identify the cargo involved.…”

Section: Discussionmentioning

confidence: 93%

“…The best known function of PI4KIIIβ is the generation of PI4P from PI (Balla and Balla, 2006;Balla, 2013). In addition, PI4KIIIβ binds to the Rab11a GTPase in a kinase-independent fashion (de Graaf et al, 2004;Polevoy et al, 2009;Burke et al, 2014) and is be involved in Rab11a-dependent control of Akt signaling (Jeganathan et al, 2008;Morrow et al, 2014) and endosome function (de Graaf et al, 2004;Polevoy et al, 2009). In our case, a catalytically inactive version of PI4KIIIβ rescues neither the reduced migration nor cell shape changes in PI4KIIIβ-deleted cells.…”

Section: Discussionmentioning

confidence: 99%

“…PI4KIIIβ is a Golgi-resident enzyme that is one of four mammalian proteins that generate PI4P from PI (Balla, 1998(Balla, , 2013. PI4 kinases have been implicated in several human cancers (Waugh, 2012) and PI4KIIIβ is a likely human oncogene based on its high expression in a subset of human breast tumours and its ability to co-operate with the Rab11a GTPase to activate signaling through Akt (Morrow et al, 2014). PI4KIIIβ and its homologues have multiple physiological roles, ranging from controlling Golgi structure in yeast to regulating male fertility and development in Drosophila (Godi et al, 1999;Polevoy et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

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Phosphatidylinositol 4-kinase III beta regulates cell shape, migration and Focal Adhesion number

Law-Vinh

Bilodeau

Jacobsen

2019

Preprint

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Cell shape is regulated by adhesion and by cytoskeletal and membrane proteins. Cell shape, adhesion and motility have a complex relationship and understanding them is important in understanding developmental patterning and diseases such as cancer. Here we show that the lipid kinase phosphatidylinositol 4-kinase III beta (PI4KIIIβ) regulates cell shape, migration and Focal Adhesion number. PI4KIIIβ generates phosphatidylinositol 4-phosphate from phosphatidylinositol and is highly expressed in a subset of human breast cancers. PI4KIIIβ and the PI4P it generates regulate a range of cellular functions, among them Golgi structure, fly fertility and Akt signaling. Here we show that loss of PI4KIIIβ expression decreases cell migration and alters cell shape in NIH3T3 fibroblasts. The changes are accompanied by an increase in the number of Focal Adhesions in cells lacking PI4KIIIβ. Furthermore, we find that PI4P-containing vesicles move to the migratory leading-edge during migration and that some of these vesicles tether to and fuse with FA. This suggests a novel regulatory role for PI4KIIIβ in cell adhesion and cell shape maintenance.

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Section: Discussionmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Phosphatidylinositol 4-kinase III beta regulates cell shape, migration and Focal Adhesion number

Law-Vinh

Bilodeau

Jacobsen

2019

Preprint

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“…Consistent with a functional role for PI4KIIIβ in cancer, ectopic PI4KIIIβ expression also disrupts three-dimensional epithelial morphogenesis of breast cells and promotes cell motility and actin remodeling 1,20,31 . Finally, our lab has reported that PI4KIIIβ is able to directly activate Akt signaling 28 .…”

Section: Introductionmentioning

confidence: 95%

“…For example, transcriptional analysis of 1992 primary human breast tumours by Curtis et al identified PI4KB, the gene encoding human PI4KIIIβ, as a cancer driver gene due to its frequent gene amplification and overexpression in primary tumour tissue 7 . Additionally, we have reported that the PI4KIIIβ protein is highly expressed in ~20% of primary human breast tumours 28 .…”

Section: Introductionmentioning

confidence: 99%

Activation of Rab11a and endocytosis by Phosphatidylinositol 4-kinase III beta promotes oncogenic signaling in breast cancer

MacDonald

Harding

Bilodeau

et al. 2020

Preprint

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Endosomes are now recognized as important sites for regulating signal transduction. Here we show that the lipid kinase phosphatidylinositol 4-kinase III beta (PI4KIIIβ) regulates both endocytic kinetics and receptor signaling in breast cancer cells. PI4KIIIβ generates phosphatidylinositol 4-phosphate from phosphatidylinositol and is highly expressed in a subset of breast cancers. However, the molecular mechanism by which PI4KIIIβ promotes breast cancer is unclear. We demonstrate that ectopic PI4KIIIβ expression increases the rates of both endocytic internalization and recycling. PI4KIIIβ deletion reduces endocytic kinetics accompanied by a concomitant decrease in activity of the Rab11a GTPase, a protein required for endocytic function. Finally, we find that PI4KIIIβ activates IGF-IRβ signaling dependent on endosome function. Regulation of endocytic function by PI4KIIIβ is independent of its kinase activity but requires interaction with the Rab11a. This suggests that PI4KIIIβ controls endosomal kinetics and signaling by directly modulating Rab11a function. Our work suggests a novel regulatory role for PI4KIIIβ in endosome function and plasma membrane receptor signaling.

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Specific sialylation of N-glycans and its novel regulatory mechanism

Gu,

Isaji

2024

Glycoconj J

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Altered glycosylation is a common feature of cancer cells. Some subsets of glycans are found to be frequently enriched on the tumor cell surface and implicated in different tumor phenotypes. Among these, changes in sialylation have long been associated with metastatic cell behaviors such as invasion and enhanced cell survival. Sialylation typically exists in three prominent linkages: α2,3, α2,6, and α2,8, catalyzed by a group of sialyltransferases. The aberrant expression of all three linkages has been related to cancer progression. The increased α2,6 sialylation on N-glycans catalyzed by β-galactoside α2,6 sialyltransferase 1 (ST6Gal1) is frequently observed in many cancers. In contrast, functions of α2,3 sialylation on N-glycans catalyzed by at least three β-galactoside α2,3-sialyltransferases, ST3Gal3, ST3Gal4, and ST3Gal6 remain elusive due to a possibility of compensating for one another. In this minireview, we briefly describe functions of sialylation and recent findings that different α2,3 sialyltransferases specifically modify target proteins, as well as sialylation regulatory mechanisms vis a complex formation among integrin α3β1, Golgi phosphoprotein 3 (GOLPH3), phosphatidylinositol 4-kinase IIα (PI4KIIα), focal adhesion kinase (FAK) and sialyltransferase, which suggests a new concept for the regulation of glycosylation in cell biology.

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The Lipid Kinase PI4KIIIβ Is Highly Expressed in Breast Tumors and Activates Akt in Cooperation with Rab11a

Abstract: Emerging evidence now implicates phosphatidylinositol 4-kinases (PI4K), enzymes that generate PI(4)P from phosphatidylinositol (PtdIns), in cancer. In this study, we investigate the role of

Cited by 36 publications

References 65 publications

Phosphatidylinositol 4-kinase III beta regulates cell shape, migration and Focal Adhesion number

Phosphatidylinositol 4-kinase III beta regulates cell shape, migration and Focal Adhesion number

Activation of Rab11a and endocytosis by Phosphatidylinositol 4-kinase III beta promotes oncogenic signaling in breast cancer

Specific sialylation of N-glycans and its novel regulatory mechanism

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