Alpha-catulin contributes to drug-resistance of melanoma by activating NF-κB and AP-1

PloS One
Birgit KreisederChristoph Wiesner

Abstract

Melanoma is the most dangerous type of skin cancer accounting for 48,000 deaths worldwide each year and an average survival rate of about 6-10 months with conventional treatment. Tumor metastasis and chemoresistance of melanoma cells are reported as the main reasons for the insufficiency of currently available treatments for late stage melanoma. The cytoskeletal linker protein α-catulin (CTNNAL1) has been shown to be important in inflammation, apoptosis and cytoskeletal reorganization. Recently, we found an elevated expression of α-catulin in melanoma cells. Ectopic expression of α-catulin promoted melanoma progression and occurred concomitantly with the downregulation of E-cadherin and the upregulation of mesenchymal genes such as N-cadherin, Snail/Slug and the matrix metalloproteinases 2 and 9. In the current study we showed that α-catulin knockdown reduced NF-κB and AP-1 activity in malignant melanoma cells. Further, downregulation of α-catulin diminished ERK phosphorylation in malignant melanoma cells and sensitized them to treatment with chemotherapeutic drugs. In particular, cisplatin treatment led to decreased ERK-, JNK- and c-Jun phosphorylation in α-catulin knockdown melanoma cells, which was accompanied by enhanced ap...Continue Reading

References

Feb 20, 1999·The Journal of Biological Chemistry·K M HeiskanenA L Nieminen
Apr 26, 2000·The Journal of Biological Chemistry·J A FrostM H Cobb
Jul 6, 2000·Journal of the National Cancer Institute·P CostantiniG Kroemer
Sep 20, 2000·The Journal of Biological Chemistry·X WangN J Holbrook
Mar 10, 2001·Nature·L Chang, M Karin
Jun 13, 2001·Oncogene·E Shaulian, M Karin
Jan 5, 2002·The Journal of Biological Chemistry·Punita Dhawan, Ann Richmond
Feb 8, 2002·Cancer Metastasis Reviews·D Grossman, D C Altieri
Jun 4, 2002·Cutis·Thomas C Yu, Maritza I Perez
Aug 20, 2003·Archives of Dermatology·Eva A HurstLynn A Cornelius
Dec 12, 2003·Nature Reviews. Cancer·Robert Eferl, Erwin F Wagner
Mar 26, 2004·European Journal of Obstetrics, Gynecology, and Reproductive Biology·G M ColpiG Piediferro
Aug 3, 2004·Oncogene·Maria José BarberàAntonio García de Herreros
Feb 3, 2005·Cell Research·Jing Liu, Anning Lin
Mar 24, 2005·Journal of the National Cancer Institute. Monographs·S J Howell, S M Shalet
Mar 25, 2005·Nature Reviews. Drug Discovery·Dong Wang, Stephen J Lippard
Jun 30, 2005·Cancer Metastasis Reviews·Katayoun I Amiri, Ann Richmond
Jul 14, 2005·Journal of Applied Toxicology : JAT·Yong Keun KimJong Min Kim
Jul 27, 2005·Molecular Carcinogenesis·Manickam VenkatramanDevarajan Karunagaran
Mar 10, 2006·Pigment Cell Research·Yukiko Ueda, Ann Richmond
Aug 11, 2006·Trends in Molecular Medicine·Wynand P Roos, Bernd Kaina
Aug 17, 2006·Genes & Development·Lynda ChinDavid E Fisher
May 18, 2007·The Journal of Investigative Dermatology·Alireza MirmohammadsadeghUlrich R Hengge
Dec 23, 2009·Current Cancer Drug Targets·P Clëzardin
Feb 1, 2011·Oncogene·L-C FanY-L Chen
Jul 21, 2011·Nature Immunology·Andrea OeckinghausSankar Ghosh
Jun 1, 2012·Molecular Cancer Research : MCR·Christine CaoAgnieszka Kobielak
Jun 27, 2012·International Journal of Cancer. Journal International Du Cancer·Birgit KreisederChristoph Wiesner

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Citations

Sep 24, 2015·Journal of Pharmacological Sciences·Xiaokun YangJinjin Wu
Aug 28, 2015·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Zhuo ZhangHua-Chuan Zheng
Feb 6, 2020·Chemical Biology & Drug Design·Sajid JalalLin Huang

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Methods Mentioned

BETA
Assay
FCS
PCR
flow cytometry
Flow Cytometric
ELISA
flow
Transfection

Software Mentioned

BioRad
CFlow plus

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