Cytoplasmic RAP1 mediates cisplatin resistance of non-small cell lung cancer

Cell Death & Disease
Lu XiaoJinbao Liu

Abstract

Cytotoxic chemotherapy agents (e.g., cisplatin) are the first-line drugs to treat non-small cell lung cancer (NSCLC) but NSCLC develops resistance to the agent, limiting therapeutic efficacy. Despite many approaches to identifying the underlying mechanism for cisplatin resistance, there remains a lack of effective targets in the population that resist cisplatin treatment. In this study, we sought to investigate the role of cytoplasmic RAP1, a previously identified positive regulator of NF-κB signaling, in the development of cisplatin resistance in NSCLC cells. We found that the expression of cytoplasmic RAP1 was significantly higher in high-grade NSCLC tissues than in low-grade NSCLC; compared with a normal pulmonary epithelial cell line, the A549 NSCLC cells exhibited more cytoplasmic RAP1 expression as well as increased NF-κB activity; cisplatin treatment resulted in a further increase of cytoplasmic RAP1 in A549 cells; overexpression of RAP1 desensitized the A549 cells to cisplatin, and conversely, RAP1 depletion in the NSCLC cells reduced their proliferation and increased their sensitivity to cisplatin, indicating that RAP1 is required for cell growth and has a key mediating role in the development of cisplatin resistance i...Continue Reading

References

Feb 20, 1992·The New England Journal of Medicine·C Schaake-KoningA Nijs
Mar 15, 1988·International Journal of Cancer. Journal International Du Cancer·W S HongP R Twentyman
Jul 1, 1996·The Journal of Cell Biology·S GrimmK Schulze-Osthoff
May 29, 2002·Oncogene·Caroline A HeckmanLinda M Boxer
Jul 2, 2003·Leukemia·P ViatourV Bours
Sep 2, 2003·Nature Reviews. Immunology·Bharat B Aggarwal
Jul 27, 2005·Molecular Carcinogenesis·Manickam VenkatramanDevarajan Karunagaran
Dec 3, 2005·Genes, Chromosomes & Cancer·Alejandro Sweet-CorderoTyler Jacks
Sep 8, 2006·The New England Journal of Medicine·Ken A OlaussenUNKNOWN IALT Bio Investigators
May 29, 2008·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Giorgio Vittorio ScagliottiDavid Gandara
Sep 9, 2008·American Journal of Respiratory and Critical Care Medicine·Pierre P MassionMargaret R Spitz
Oct 14, 2009·Molecular and Cellular Biochemistry·Sahdeo PrasadBharat B Aggarwal
Jul 14, 2010·Nature Cell Biology·Hsiangling TeoVinay Tergaonkar
Feb 25, 2011·Nature Reviews. Cancer·Paula Martínez, María A Blasco
Mar 19, 2011·Cell Death and Differentiation·P N Kelly, A Strasser
Mar 29, 2011·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Shiau-Chuen CheahMohd Rais Mustafa
Dec 17, 2014·Journal of the National Cancer Institute·Lauren G AoudeNicholas K Hayward
Feb 25, 2015·Nature Reviews. Cancer·Laurence H PearlFrances M G Pearl
Jan 1, 2015·Nature Reviews. Disease Primers·Cesare GridelliRafael Rosell

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Citations

Feb 9, 2018·Molecular and Cellular Biochemistry·Naveen KumarSeema Sehrawat
Jan 10, 2019·International Journal of Molecular Sciences·Jun-Hua NieJia Liu
Apr 13, 2019·Journal of Experimental & Clinical Cancer Research : CR·Yuning LiaoHongbiao Huang
Jun 6, 2020·Frontiers in Immunology·Maria E ReyesPriscilla Brebi
Sep 11, 2020·Biomedicines·Chin-King LooiChun-Wai Mai
Jul 4, 2020·Cancer Research·Foteinos-Ioannis D DimitrakopoulosHaralabos P Kalofonos
Jul 1, 2021·Science Signaling·Dmitri Churikov, Vincent Géli
Aug 8, 2021·Cancers·Anxo Rio-VilariñoArancha Cebrián

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