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Oncogene. 2016 Jun 23;35(25):3314-23. doi: 10.1038/onc.2015.393. Epub 2015 Oct 12.

PDK1 promotes tumor growth and metastasis in a spontaneous breast cancer model.

Author information

1
School of Medicine, Tsinghua University, Beijing, China.
2
Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing, China.
3
Center of Animal Facility, Tsinghua University, Beijing, China.

Abstract

Because malignant cells have altered, usually accelerated, energy consumption, targeting metabolic signaling represents a prevailing strategy for tumor therapy. Phosphoinositide-dependent kinase 1 (PDK1) is a proximal signaling molecule of phosphatidylinositol 3-kinase, which is required for metabolic activation. It is still lacking definitive evidence whether inactivation of PDK1 can overwhelm tumorigenesis in vivo. Herein we revealed that mammary-specific ablation of PDK1 could delay tumor initiation, progression and metastasis in a spontaneous mouse tumor model. We also demonstrated that inducible deletion of PDK1 could noticeably shrink the growing breast tumors. However, a small portion of PDK1-deficient tumorigenic cells eventually established tumor lesions, albeit at a relatively later phase, most likely owing to compensatory upregulation of extracellular signal-regulated kinase 1/2 (Erk1/2) phosphorylation. Consequently, simultaneous inhibition of PDK1 and Erk1/2 impeded the survival of breast cancer cells. Thus we identify PDK1 as a potential therapeutic target for breast cancer, particularly in combination with an Erk1/2 inhibitor.

PMID:
26455327
DOI:
10.1038/onc.2015.393
[Indexed for MEDLINE]

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