A feed-forward loop involving protein kinase Calpha and microRNAs regulates tumor cell cycle.

Cancer Research
Ezra E W CohenMarsha Rich Rosner

Abstract

Protein kinase Calpha (PKCalpha) has been implicated in cancer, but the mechanism is largely unknown. Here, we show that PKCalpha promotes head and neck squamous cell carcinoma (SCCHN) by a feed-forward network leading to cell cycle deregulation. PKCalpha inhibitors decrease proliferation in SCCHN cell lines and xenografted tumors. PKCalpha inhibition or depletion in tumor cells decreases DNA synthesis by suppressing extracellular signal-regulated kinase phosphorylation and cyclin E synthesis. Additionally, PKCalpha down-regulates miR-15a, a microRNA that directly inhibits protein synthesis of cyclin E, as well as other cell cycle regulators. Furthermore, both PKCalpha and cyclin E protein expression are increased in primary tumors, and PKCalpha inversely correlates with miR-15a expression in primary tumors. Finally, PKCalpha is associated with poor prognosis in SCCHN. These results identify PKCalpha as a key regulator of SCCHN tumor cell growth by a mechanism involving activation of mitogen-activated protein kinase, an initiator of the cell cycle, and suppression of miR-15a, an inhibitor of DNA synthesis. Although the specific components may be different, this type of feed-forward loop network, consisting of a stimulus that ac...Continue Reading

References

May 6, 1996·Biochemical and Biophysical Research Communications·N NakaigawaS Ohno
Aug 25, 2000·American Journal of Physiology. Lung Cellular and Molecular Physiology·E C DempseyR O Messing
Dec 6, 2000·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·R C AntonP T Cagle
Apr 20, 2001·Proceedings of the National Academy of Sciences of the United States of America·V G TusherG Chu
Jan 5, 2002·Expert Opinion on Investigational Drugs·P G Goekjian, M R Jirousek
Nov 16, 2002·Proceedings of the National Academy of Sciences of the United States of America·George Adrian CalinCarlo M Croce
Dec 18, 2002·The Journal of Investigative Dermatology·Shalini S TibudanMitchell F Denning
May 23, 2003·Journal of Biochemistry·Takaaki Hirai, Kazuhiro Chida
Jun 10, 2003·The Journal of Biological Chemistry·Jae-Won Soh, I Bernard Weinstein
Jun 18, 2003·Genomics·Kwang S SuhStuart H Yuspa
Jan 14, 2005·Journal of Cellular Physiology·Arianna BottoniEttore C degli Uberti
Jan 22, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Christophe CataissonStuart H Yuspa
Apr 20, 2005·Oncogene·Harry C Hwang, Bruce E Clurman
Jun 10, 2005·Nature·Kathryn A O'DonnellJoshua T Mendell
Sep 17, 2005·Proceedings of the National Academy of Sciences of the United States of America·Amelia CimminoCarlo M Croce
Oct 4, 2005·Proceedings of the National Academy of Sciences of the United States of America·Aravind SubramanianJill P Mesirov
Dec 24, 2005·The Journal of Investigative Dermatology·Sirosh M BokhariVaishali Chaudhuri
Feb 10, 2006·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Robbert J C SlebosChristine H Chung
Sep 13, 2006·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Claudia RoldoCarlo M Croce
Dec 1, 2006·The Journal of Biological Chemistry·Yannick SylvestrePascal Chartrand
Dec 1, 2006·The Journal of Biological Chemistry·Keith WoodsScott M Hammond
Dec 14, 2006·International Journal of Cancer. Journal International Du Cancer·Wei WuJianjun Chen
Jan 2, 2007·Trends in Cell Biology·Ramesh S PillaiWitold Filipowicz
Jan 16, 2007·Molecular Cell·Yan GengPiotr Sicinski
Jan 24, 2007·Molecular and Cellular Biology·Peter S LinsleyLee Lim
Mar 27, 2007·Nature Reviews. Cancer·Erin M Griner, Marcelo G Kazanietz
Apr 27, 2007·Clinica Chimica Acta; International Journal of Clinical Chemistry·Trang-Tiau WuJer-Yuh Liu
May 19, 2007·Nature Reviews. Genetics·Uri Alon
May 22, 2007·Cell·George-Lucian MoldovanStefan Jentsch
Jun 8, 2007·Nature·Lin HeGregory J Hannon
Jul 17, 2007·Annual Review of Genetics·R A Sclafani, T M Holzen

❮ Previous
Next ❯

Citations

Dec 11, 2013·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·V P Sivadas, S Kannan
Feb 10, 2010·Proceedings of the National Academy of Sciences of the United States of America·Elena A VidalRodrigo A Gutiérrez
Sep 10, 2010·The Journal of Biological Chemistry·Yanfei XuAlex C Minella
Sep 30, 2010·Molecular Cancer Therapeutics·Wen-Liang KuoEzra Eddy Wyssam Cohen
Feb 17, 2010·BMC Systems Biology·An-Yuan GuoZhongming Zhao
Jul 26, 2012·PLoS Computational Biology·Jingchun SunZhongming Zhao
May 16, 2014·Annals of Oncology : Official Journal of the European Society for Medical Oncology·L De CeccoL Licitra
Jan 1, 2010·Journal of Oncology·Li-Hsin ChenWen-Liang Lo
Nov 22, 2013·International Journal of Dentistry·Keziah JohnCamile S Farah
Dec 22, 2011·Cell Cycle·Ka Tat SiuAlex C Minella
Apr 14, 2010·Experimental Cell Research·Ditte C AndersenSøren P Sheikh
Mar 30, 2017·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·V G Manasa, S Kannan
Jun 22, 2018·Omics : a Journal of Integrative Biology·Tania IslamNurul Haque Mollah
Mar 10, 2010·Head & Neck·Nham TranBarbara Rose
Nov 10, 2013·Cancers·Prashant Kumar Singh, Moray J Campbell
Apr 20, 2011·Journal of Cellular Biochemistry·G ReshmiM Radhakrishna Pillai
Mar 26, 2011·Molecular BioSystems·Ujjwal MaulikSanghamitra Bandyopadhyay
Nov 1, 2018·Journal of Experimental & Clinical Cancer Research : CR·Miyong YunYoung-Gyu Eun
Oct 12, 2019·Experimental and Therapeutic Medicine·Yanchun LiuBingzhi Yu
Dec 23, 2011·Journal of Oral Pathology & Medicine : Official Publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology·Mario Pérez-SayánsAbel García-García
Jan 30, 2013·Cancer Biology & Therapy·Anália do CarmoMaria Celeste Lopes
Mar 20, 2018·International Urology and Nephrology·Yulian MytsykManyuk Lubov
Dec 11, 2014·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Michaela K KeckTanguy Y Seiwert
Jun 13, 2013·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Alain C JungBohdan Wasylyk
Feb 5, 2021·Endocrinology·Annarita NappiDomenico Salvatore
Dec 12, 2020·Advances in Biological Regulation·Adrian R Black, Jennifer D Black

❮ Previous
Next ❯

Related Concepts

Related Feeds

Carcinoma, Squamous Cell

Basal cell carcinoma is a form of malignant skin cancer found on the head and neck regions and has low rates of metastasis. Discover the latest research on basal cell carcinoma here.