Immunohistochemical analysis of PDK1 expression in breast cancer

Background3-phosphoinositide-dependent protein kinase-1 (PDK1) functions downstream of phosphoinositide 3-kinase (PIK3) and activates members of the AGC family of protein kinases that are known to play crucial roles in physiological processes associated with cell metabolism, growth, proliferation and survival. Changes in the expression and activity of PDK1 and several AGC kinases have been linked to human disease, including cancer.MethodsWe used immunohistochemical analysis to determine PDK1 expression in 241 tumors from patients with breast cancer in which we had previously analyzed PIK3CA mutation status.ResultsModerate or high expression of PDK1 was observed in 213 of the 241 cases (88%). There was no correlation between PIK3CA mutation status and PDK1 overexpression.ConclusionOur findings indicate that PDK1 is independently activated in breast cancer and not only as part of the PIK3CA pathway, suggesting that PDK1 plays a specific and distinct role from the canonical PIK3/Akt pathway and promotes oncogenesis independently of AKT. Our data implicate PDK-1 and downstream components of the PDK-1 signaling pathway as promising therapeutic targets for the treatment of breast cancer.

• Publication year

  2014

• Venue

  Diagnostic Pathology

• Publication date

  2014-04-16

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1186/1746-1596-9-82PMID 24739482PMCID 4005628
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• The PDK1 master kinase is over-expressed in acute myeloid leukemia and promotes PKC-mediated survival of leukemic blasts

  2014cited by this paper
• Analysis of PIK3CA Mutations in Breast Cancer Subtypes

  2014cited by this paper
• Overexpression of CARM1 in breast cancer is correlated with poorly characterized clinicopathologic parameters and molecular subtypes

  2013cited by this paper
• Selective requirement of PI3K/PDK1 signaling for Kras oncogene-driven pancreatic cell plasticity and cancer.

  2013cited by this paper
• Impact of tumor heterogeneity on disease-free survival in a series of 368 patients treated for a breast cancer

  2013cited by this paper
• NY-ESO-1 antibody as a novel tumour marker of gastric cancer

  2013cited by this paper
• PDK1 inhibition is a novel therapeutic target in multiple myeloma

  2012cited by this paper
• B55β-associated PP2A complex controls PDK1-directed myc signaling and modulates rapamycin sensitivity in colorectal cancer.

  2010cited by this paper
• 3-Phosphoinositide-dependent kinase 1 potentiates upstream lesions on the phosphatidylinositol 3-kinase pathway in breast carcinoma.

  2009cited by this paper
• AKT-independent signaling downstream of oncogenic PIK3CA mutations in human cancer.

  2009cited by this paper
• The role of PKC and PDK1 in monocyte lineage specification by Ras.

  2007cited by this paper
• Hypomorphic mutation of PDK1 suppresses tumorigenesis in PTEN(+/-) mice.

  2005cited by this paper
• Cancer Management and Research Dovepress 3-phosphoinositide-dependent Protein Kinase-1 as an Emerging Target in the Management of Breast Cancer

  year unknowncited by this paper

• Rational design of next-generation PDK1 modulators: Addressing selectivity and resistance through molecular insights - A medicinal chemistry perspective.

  2025cites this paper
• Nanomaterials‐mediated glycolysis rewriting to potentiate tumor immunotherapy

  2025cites this paper
• 3-Phosphoinositide-Dependent Kinase 1 as a Therapeutic Target for Treating Diabetes.

  2024cites this paper
• A PD‐L1 Antibody‐Conjugated PAMAM Dendrimer Nanosystem for Simultaneously Inhibiting Glycolysis and Promoting Immune Response in Fighting Breast Cancer

  2023cites this paper
• Investigation of the Anticancer Effect of α-Aminophosphonates and Arylidine Derivatives of 3-Acetyl-1-aminoquinolin-2(1H)-one on the DMBA Model of Breast Cancer in Albino Rats with In Silico Prediction of Their Thymidylate Synthase Inhibitory Effect

  2022cites this paper
• A cuproptosis-related genes signature associated with prognosis and immune cell infiltration in osteosarcoma

  2022cites this paper
• Possible involvement of the Hedgehog and PDPK1–Akt pathways in the growth and migration of small-cell lung cancer

  2021cites this paper
• The landscape of PDK1 in Breast Cancer Running title: PDK1 in breast cancer

  2021cites this paper
• The Landscape of PDK1 in Breast Cancer

  2021cites this paper
• Expression and clinical significance of PDK family in breast cancer based on data mining.

  2021cites this paper
• SPRY4-IT1 promotes survival of colorectal cancer cells through regulating PDK1-mediated glycolysis

  2020cites this paper
• Profiles of immune cell infiltration and immune-related genes in the tumor microenvironment of osteosarcoma

  2020cites this paper
• ESM-1 Overexpression is Involved in Increased Tumorigenesis of Radiotherapy-Resistant Breast Cancer Cells

  2020cites this paper
• Quadruple-negative breast cancer: novel implications for a new disease

  2020cites this paper
• Tumor suppressive effect of Artemisia annua extract in 7, 12-dimethylbenz[a]anthracene-induced breast cancer in Wistar rats

  2020cites this paper
• Expression of PDK-1 and DMBT1 in the thyroid carcinoma and its clinicopathological significance

  2019cites this paper
• Investigation of expressions of PDK1, PLK1 and c‐Myc in diffuse large B‐cell lymphoma

  2019cites this paper
• Spatial alterations of De Novo purine biosynthetic enzymes by Akt-independent PDK1 signaling pathways

  2018cites this paper
• Design, synthesis, crystal structures and anticancer activity of 4-substituted quinolines to target PDK1.

  2018cites this paper
• Immunohistochemical detection of gremlin-2 protein in hen ovarian prehierarchical follicle cells

  2018cites this paper
• 3-Phosphoinositide Dependent Protein Kinase-1 (PDK-1) Promotes Migration and Invasion in Gastric Cancer Cells Through Activating the NF-κB Pathway

  2017cites this paper
• Role for loss of nuclear PTEN in a harbinger of brain metastases.

  2017cites this paper
• MicroRNA‐379 suppresses osteosarcoma progression by targeting PDK1

  2016cites this paper
• Overexpression of 3-phosphoinositide-dependent protein kinase-1 is associated with prognosis of gastric carcinoma

  2016cites this paper
• PDK1 is Expressed in Ovarian Serous Carcinoma and Correlates with Improved Survival in High-grade Tumors.

  2015cites this paper
• Upregulation of PDK1 associates with poor prognosis in esophageal squamous cell carcinoma with facilitating tumorigenicity in vitro

  2014cites this paper