The phosphorylation status of PIP5K1C at serine 448 can be predictive for invasive ductal carcinoma of the breast


The cover for issue 91 of Oncotarget features Figure 6, "PKD1 expression status and phosphorylation of PIP5K1C at S448 correlate in patient samples of TNBC," by Durand, et al.

By comparing normal breast tissue to carcinoma in situ and invasive ductal carcinoma subtypes, Durand et al. show that the phosphorylation status of PIP5K1C at serine residue 448 can be predictive for breast cancer progression to an aggressive phenotype, while PIP5K1C expression levels are not indicative for this event.

Dr. Peter Storz from the Department of Cancer Biology, Mayo Clinic Comprehensive Cancer Center, Mayo Clinic, Jacksonville, FL 32224, USA said, "The family of phosphatidylinositol-4-phosphate 5-kinase type-1 (PIP5K1) lipid kinases consists of three isoforms, PIP5K1A, PIP5K1B and PIP5K1C, each of which exists in multiple alternatively spliced variants."

Altered focal adhesion (FA) dynamics due to decrease in PIP5K1C activity or expression has been linked to increased cell migration and invasion.

PIP5K1C localization to FA is negatively-regulated by p35/Cdk5-mediated phosphorylation at S650; and PIP5K1C degradation is regulated by phosphorylation through p70S6K1 at threonine 553 and serine 555, while its lipid kinase activity is inhibited after phosphorylation through protein kinase D (PKD) at serine 448.

Figure 1: The expression of PIP5K1C is not predictive for breast cancer survival or subtype.

In breast cancer all three PIP5K1 isoforms have been implicated in regulating cancer cell survival and proliferation during tumor formation.

Durand et al. investigated if expression of PIP5K1C or its phosphorylation status at serine 448 can be indicative for invasive breast cancers.

Their data suggest that PKD1 expression levels in tumors correlate with PIP5K1C phosphorylation at serine 448, and that the PIP5K1C phosphorylation at this residue may be a predictive marker for progression to an aggressive phenotype.

The Storz research team concluded, "Since phosphorylation of this site is mediated by PKD1, a kinase that previously was linked to maintain the epithelial phenotype and decrease of migratory potential of cancer cells, we predict that the phosphorylation status of this residue may serve as an indicator of aggressiveness of breast tumors."

Full text - https://www.oncotarget.com/article/26357/text/

Correspondence to - Peter Storz, email: [email protected]

Keywords - PIP5K1C; breast cancer; invasive phenotype; phosphorylation

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