PKD1 is a potential biomarker and therapeutic target in triple-negative breast cancer
<p dir="ltr">Protein Kinase D1 (PKD1) is a serine/threonine kinase encoded by the <i>PRKD1</i> gene. PKD1 has been previously shown to be a prognostic factor in ERα+ tamoxifen-resistant breast tumors and PKD1 overexpression confers estrogen independence to ERα+ MCF7 cells...
محفوظ في:
| المؤلف الرئيسي: | |
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| مؤلفون آخرون: | , , , , , , , , , , |
| منشور في: |
2018
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| الملخص: | <p dir="ltr">Protein Kinase D1 (PKD1) is a serine/threonine kinase encoded by the <i>PRKD1</i> gene. PKD1 has been previously shown to be a prognostic factor in ERα+ tamoxifen-resistant breast tumors and PKD1 overexpression confers estrogen independence to ERα+ MCF7 cells. In the present study, our goal was to determine whether PKD1 is a prognostic factor and/or a relevant therapeutic target in breast cancer. We analyzed <i>PRKD1</i> mRNA levels in 527 primary breast tumors. We found that high <i>PRKD1</i> mRNA levels were significantly and independently associated with a low metastasis-free survival in the whole breast cancer population and in the triple-negative breast cancer (TNBC) subtype specifically. High <i>PRKD1</i> mRNA levels were also associated with a low overall survival in TNBC. We identified novel PKD1 inhibitors and assessed their antitumor activity <i>in vitro</i> in TNBC cell lines and <i>in vivo</i> in a TNBC patient-derived xenograft (PDX) model. Pharmacological inhibition and siRNA-mediated depletion of PKD1 reduced colony formation in MDA-MB-436 TNBC cells. PKD1 inhibition also reduced tumor growth <i>in vivo</i> in a TNBC PDX model. Together, these results establish PKD1 as a poor prognostic factor and a potential therapeutic target in TNBC.</p><h2>Other Information</h2><p dir="ltr">Published in: Oncotarget<br>License: <a href="https://creativecommons.org/licenses/by/4.0/" target="_blank">https://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.18632/oncotarget.25292" target="_blank">https://dx.doi.org/10.18632/oncotarget.25292</a></p> |
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