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Literature DB >> 26977885

Protein Kinase Cι Drives a NOTCH3-dependent Stem-like Phenotype in Mutant KRAS Lung Adenocarcinoma.

Syed A Ali¹, Verline Justilien¹, Lee Jamieson¹, Nicole R Murray¹, Alan P Fields².

Abstract

We report that the protein kinase Cι (PKCι) oncogene controls expression of NOTCH3, a key driver of stemness, in KRAS-mediated lung adenocarcinoma (LADC). PKCι activates NOTCH3 expression by phosphorylating the ELF3 transcription factor and driving ELF3 occupancy on the NOTCH3 promoter. PKCι-ELF3-NOTCH3 signaling controls the tumor-initiating cell phenotype by regulating asymmetric cell division, a process necessary for tumor initiation and maintenance. Primary LADC tumors exhibit PKCι-ELF3-NOTCH3 signaling, and combined pharmacologic blockade of PKCι and NOTCH synergistically inhibits tumorigenic behavior in vitro and LADC growth in vivo demonstrating the therapeutic potential of PKCι-ELF3-NOTCH3 signal inhibition to more effectively treat KRAS LADC.

Entities: CellLine Chemical Disease Gene Mutation Species

Keywords: ELF3; KRAS-driven lung adenocarcinoma; NOTCH signaling; protein kinase Cι; therapeutic intervention

Mesh：

Substances：

Year: 2016 PMID： 26977885 PMCID： PMC4795153 DOI： 10.1016/j.ccell.2016.02.012

Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743

62 in total

1. Atypical protein kinase Ciota plays a critical role in human lung cancer cell growth and tumorigenicity.

Authors: Roderick P Regala; Capella Weems; Lee Jamieson; John A Copland; E Aubrey Thompson; Alan P Fields
Journal: J Biol Chem Date: 2005-07-01 Impact factor: 5.157

2. Cancer stem cells--perspectives on current status and future directions: AACR Workshop on cancer stem cells.

Authors: Michael F Clarke; John E Dick; Peter B Dirks; Connie J Eaves; Catriona H M Jamieson; D Leanne Jones; Jane Visvader; Irving L Weissman; Geoffrey M Wahl
Journal: Cancer Res Date: 2006-09-21 Impact factor: 12.701

3. Retention of prominin in microvilli reveals distinct cholesterol-based lipid micro-domains in the apical plasma membrane.

Authors: K Röper; D Corbeil; W B Huttner
Journal: Nat Cell Biol Date: 2000-09 Impact factor: 28.824

Review 4. Dividing cellular asymmetry: asymmetric cell division and its implications for stem cells and cancer.

Authors: Ralph A Neumüller; Juergen A Knoblich
Journal: Genes Dev Date: 2009-12-01 Impact factor: 11.361

5. p40 is the best marker for diagnosing pulmonary squamous cell carcinoma: comparison with p63, cytokeratin 5/6, desmocollin-3, and sox2.

Authors: Takahiro Tatsumori; Koji Tsuta; Kyohei Masai; Tomoaki Kinno; Tomoko Taniyama; Akihiko Yoshida; Kenji Suzuki; Hitoshi Tsuda
Journal: Appl Immunohistochem Mol Morphol Date: 2014 May-Jun

Review 6. Targeting the oncogenic protein kinase Ciota signalling pathway for the treatment of cancer.

Authors: A P Fields; L A Frederick; R P Regala
Journal: Biochem Soc Trans Date: 2007-11 Impact factor: 5.407

7. Targeted therapy using novel agents in the treatment of non-small-cell lung cancer.

Authors: Roy S Herbst
Journal: Clin Lung Cancer Date: 2002-03 Impact factor: 4.785

8. Matrix metalloproteinase-10 is a critical effector of protein kinase Ciota-Par6alpha-mediated lung cancer.

Authors: L A Frederick; J A Matthews; L Jamieson; V Justilien; E A Thompson; D C Radisky; A P Fields
Journal: Oncogene Date: 2008-04-21 Impact factor: 9.867

9. Oncogenic NRAS signaling differentially regulates survival and proliferation in melanoma.

Authors: Lawrence N Kwong; James C Costello; Huiyun Liu; Shan Jiang; Timothy L Helms; Aliete E Langsdorf; David Jakubosky; Giannicola Genovese; Florian L Muller; Joseph H Jeong; Ryan P Bender; Gerald C Chu; Keith T Flaherty; Jennifer A Wargo; James J Collins; Lynda Chin
Journal: Nat Med Date: 2012-09-16 Impact factor: 53.440

Review 10. Notch signaling in serous ovarian cancer.

Authors: Jolijn W Groeneweg; Rosemary Foster; Whitfield B Growdon; René H M Verheijen; Bo R Rueda
Journal: J Ovarian Res Date: 2014-11-04 Impact factor: 4.234

43 in total

1. Protein kinase Cι promotes UBF1-ECT2 binding on ribosomal DNA to drive rRNA synthesis and transformed growth of non-small-cell lung cancer cells.

Authors: Verline Justilien; Kayla C Lewis; Kayleah M Meneses; Lee Jamieson; Nicole R Murray; Alan P Fields
Journal: J Biol Chem Date: 2020-04-29 Impact factor: 5.157

Protein Kinase Cι Drives a NOTCH3-dependent Stem-like Phenotype in Mutant KRAS Lung Adenocarcinoma.

1. Atypical protein kinase Ciota plays a critical role in human lung cancer cell growth and tumorigenicity.

2. Cancer stem cells--perspectives on current status and future directions: AACR Workshop on cancer stem cells.

3. Retention of prominin in microvilli reveals distinct cholesterol-based lipid micro-domains in the apical plasma membrane.

Review 4. Dividing cellular asymmetry: asymmetric cell division and its implications for stem cells and cancer.

5. p40 is the best marker for diagnosing pulmonary squamous cell carcinoma: comparison with p63, cytokeratin 5/6, desmocollin-3, and sox2.

Review 6. Targeting the oncogenic protein kinase Ciota signalling pathway for the treatment of cancer.

7. Targeted therapy using novel agents in the treatment of non-small-cell lung cancer.

8. Matrix metalloproteinase-10 is a critical effector of protein kinase Ciota-Par6alpha-mediated lung cancer.

9. Oncogenic NRAS signaling differentially regulates survival and proliferation in melanoma.

Review 10. Notch signaling in serous ovarian cancer.

1. Protein kinase Cι promotes UBF1-ECT2 binding on ribosomal DNA to drive rRNA synthesis and transformed growth of non-small-cell lung cancer cells.

Review 2. The Role of Notch3 in Cancer.

Review 3. Protein kinase C as a tumor suppressor.

4. Inhibition of MEK, a canonical KRAS pathway effector in KRAS mutant NSCLC.

5. Targeting oncogenic protein kinase Cι for treatment of mutant KRAS LADC.

6. Protein kinase Cι: A versatile oncogene in the lung.

7. Oncogenic PKCι decides tumor-initiating cell fate.

Review 8. The Dual Roles of the Atypical Protein Kinase Cs in Cancer.

9. Activation of atypical protein kinase C by sphingosine 1-phosphate revealed by an aPKC-specific activity reporter.

10. Protein Kinase Cι and Wnt/β-Catenin Signaling: Alternative Pathways to Kras/Trp53-Driven Lung Adenocarcinoma.