GKN2 promotes oxidative stress-induced gastric cancer cell apoptosis via the Hsc70 pathway

Journal of Experimental & Clinical Cancer Research : CR
Ziqiang ZhangJianjun Du

Abstract

The GKN2 is a secretory protein, whose levels decrease in gastric cancer. The present study aimed to investigate the expression, function and mechanism of action of GKN2 in gastric cancer. Molecular biology assays were performed to elucidate the function and underlying mechanisms of GKN2 in gastric cancer under stress-induced condition in vivo and in vitro. Clinical specimens were used to assess the correlation of GKN2 and prognosis. We found that overexpression of GKN2 significantly enhanced apoptosis and growth arrest in vitro. GKN2 expression increased in gastric cancer cells exposed to hydrogen peroxide and promoted reactive oxygen species-induced mitochondrial dysfunction and resulted in increased cell apoptosis via inhibition of NF-κB signaling pathway and activation of JNK signaling pathway through the direct interaction of GKN2 with Hsc70. Trefoil factor 1 might contribute to the tumor suppressing effects of GKN2. MiR-216a downregulated GKN2 expression. GKN2 also inhibited xenograft tumor growth and was an independent and significant prognostic factor for patients with gastric cancer treated with oxaliplatin. Taken together, our data indicate that GKN2 may increase sensitivity of GC cells to the drugs which increase ROS...Continue Reading

References

Jul 10, 2003·American Journal of Physiology. Gastrointestinal and Liver Physiology·Terence E MartinF Gary Toback
Apr 2, 2005·Nature Reviews. Molecular Cell Biology·Martin Holcik, Nahum Sonenberg
Dec 13, 2005·Cell Death and Differentiation·H NakanoK Okumura
Jun 7, 2006·Free Radical Research·Yoshiro SaitoEtsuo Niki
Aug 29, 2006·Biochemical Pharmacology·Andy WullaertRudi Beyaert
Jun 20, 2007·Antioxidants & Redox Signaling·Michael J MorganZhenggang Liu
Feb 28, 2008·Cell Research·Michael J MorganZheng-gang Liu
Apr 14, 2009·Antioxidants & Redox Signaling·Derick HanNeil Kaplowitz
Jul 31, 2009·Oncogene·J Yu, L Zhang
Sep 15, 2009·BMC Research Notes·Joel HedlundBengt Persson
Feb 9, 2010·Gastroenterology·Trevelyan R MenheniottAndrew S Giraud
Jul 24, 2010·Molecules and Cells·Michael J Morgan, Zheng-Gang Liu
Oct 23, 2010·Molecular Cell·Keith A SpriggsAnne E Willis
Nov 17, 2012·American Journal of Physiology. Gastrointestinal and Liver Physiology·Trevelyan R MenheniottAndrew S Giraud
Mar 9, 2013·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Hongping XiaKam M Hui
May 30, 2013·Physiological Genomics·Jessica H GeahlenJason C Mills
Jan 1, 2014·Wiley Interdisciplinary Reviews. RNA·Botao Liu, Shu-Bing Qian
Feb 27, 2014·Asian Pacific Journal of Cancer Prevention : APJCP·Joanna Kruk, Ewa Duchnik
Jun 25, 2014·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Ren-Tao WangHua Jin
Oct 8, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·Nicola J ManeyCatharien M U Hilkens
Dec 18, 2014·Nature Chemical Biology·Samuel E Weinberg, Navdeep S Chandel
Feb 6, 2015·CA: a Cancer Journal for Clinicians·Lindsey A TorreAhmedin Jemal
Jan 26, 2016·CA: a Cancer Journal for Clinicians·Wanqing ChenJie He
Mar 15, 2016·The Journal of Clinical Investigation·Trevelyan R MenheniottAndrew S Giraud
Oct 27, 2016·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Jin DaiJie Chen
Feb 6, 2017·Gastric Cancer : Official Journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association·Olga KimWon Sang Park
Jan 9, 2018·Biochemical and Biophysical Research Communications·Jie ZhuJie Liu

❮ Previous
Next ❯

Methods Mentioned

BETA
transfection
Protein Assay
Assay
flow cytometry
xenograft
Antibody Array
co-immunoprecipitation
immunoprecipitation
ubiquitination
Co-IP

Software Mentioned

GraphPad Prism
GraphPad

Related Concepts

Related Feeds

Apoptosis in Cancer

Apoptosis is an important mechanism in cancer. By evading apoptosis, tumors can continue to grow without regulation and metastasize systemically. Many therapies are evaluating the use of pro-apoptotic activation to eliminate cancer growth. Here is the latest research on apoptosis in cancer.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis