X-linked inhibitor of apoptosis protein mediates tumor cell resistance to antibody-dependent cellular cytotoxicity

Cell Death & Disease
M K EvansGayathri R Devi

Abstract

Inflammatory breast cancer (IBC) is the deadliest, distinct subtype of breast cancer. High expression of epidermal growth factor receptors [EGFR or human epidermal growth factor receptor 2 (HER2)] in IBC tumors has prompted trials of anti-EGFR/HER2 monoclonal antibodies to inhibit oncogenic signaling; however, de novo and acquired therapeutic resistance is common. Another critical function of these antibodies is to mediate antibody-dependent cellular cytotoxicity (ADCC), which enables immune effector cells to engage tumors and deliver granzymes, activating executioner caspases. We hypothesized that high expression of anti-apoptotic molecules in tumors would render them resistant to ADCC. Herein, we demonstrate that the most potent caspase inhibitor, X-linked inhibitor of apoptosis protein (XIAP), overexpressed in IBC, drives resistance to ADCC mediated by cetuximab (anti-EGFR) and trastuzumab (anti-HER2). Overexpression of XIAP in parental IBC cell lines enhances resistance to ADCC; conversely, targeted downregulation of XIAP in ADCC-resistant IBC cells renders them sensitive. As hypothesized, this ADCC resistance is in part a result of the ability of XIAP to inhibit caspase activity; however, we also unexpectedly found that re...Continue Reading

References

Jul 4, 2001·Nature Reviews. Molecular Cell Biology·M Holcik, R G Korneluk
Mar 29, 2002·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Francisco J EstevaGabriel N Hortobagyi
Jan 1, 2004·The Journal of Biological Chemistry·Jennifer LewisColin S Duckett
Nov 9, 2004·Trends in Immunology·Alberto MantovaniMassimo Locati
Oct 4, 2005·Proceedings of the National Academy of Sciences of the United States of America·Aravind SubramanianJill P Mesirov
May 10, 2006·Proceedings of the National Academy of Sciences of the United States of America·Wenle XiaNeil L Spector
Mar 14, 2007·Annals of Oncology : Official Journal of the European Society for Medical Oncology·N CabiogluM Cristofanilli
Oct 20, 2007·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·David B SeligsonBenjamin Bonavida
Apr 2, 2008·Nature Reviews. Immunology·Reinhold FörsterAntal Rot
Aug 19, 2008·Genes & Development·Andrew J SchileHermann Steller
Nov 13, 2008·International Journal of Cancer. Journal International Du Cancer·Simone Fulda
Mar 4, 2009·Cellular & Molecular Immunology·L Chávez-GalánR Lascurain
Jul 11, 2009·Cell Death and Differentiation·S Galbán, C S Duckett
Jan 16, 2010·Cell Death and Differentiation·S P CullenS J Martin
Jan 27, 2010·BMC Biology·Nicholas MatlukJoseph M Verdi
Jun 12, 2010·Immunological Reviews·Inna S AfoninaSeamus J Martin
Aug 5, 2010·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Hamid Kashkar
Oct 21, 2010·CA: a Cancer Journal for Clinicians·Fredika M RobertsonMassimo Cristofanilli
Dec 29, 2010·Cell Research·Michael J Morgan, Zheng-gang Liu
May 12, 2011·Breast Cancer Research and Treatment·Katherine M AirdGayathri R Devi
Sep 29, 2011·Advances in Experimental Medicine and Biology·Mario PerlMarkus Huber-Lang
Mar 23, 2012·Nature Reviews. Cancer·Drew M Pardoll
Apr 18, 2012·Molecular Cancer Therapeutics·Jennifer L AllensworthGayathri R Devi
Jul 28, 2012·Trends in Immunology·Shawn T BeugRobert G Korneluk
Jan 24, 2013·PloS One·Smita NairGayathri R Devi

❮ Previous
Next ❯

Citations

Jul 11, 2006·Progress in Neurobiology·Peng YangTheo Hagg
Nov 13, 2018·NPJ Systems Biology and Applications·Greta Del MistroDagmar Kulms
Dec 28, 2018·Proceedings of the National Academy of Sciences of the United States of America·Federico BocciMohit Kumar Jolly
Aug 1, 2020·Investigative Ophthalmology & Visual Science·Sarah J WassmerCatherine Tsilfidis
Apr 11, 2020·Cancers·Christian Sordo-BahamondeSegundo Gonzalez
Feb 6, 2020·Journal of Biomedical Science·Chun Hei Antonio CheungEuphemia Leung
Mar 6, 2018·The Journal of Infectious Diseases·Haiju ZhangDeling Yin
Jun 2, 2018·Cancer Immunology, Immunotherapy : CII·Jun YinJohn O Richards
Jul 24, 2020·Antibodies·David Zahavi, Louis Weiner
Nov 4, 2020·Biomolecules·Huailu Tu, Max Costa
Sep 29, 2021·Breast Cancer Research : BCR·Anastasia A IonkinaJennifer A Prescher

❮ Previous
Next ❯

Methods Mentioned

BETA
ubiquitination
and
xenografts
transfection
transfections
fluorescence-activated cell sorting
leukapheresis
flow cytometry
Assay
protein assay

Software Mentioned

Graphpad Prism
FlowJO
ImageJ
NIH ImageJ
GSEA

Related Concepts

Related Feeds

Adrenocortical Carcinoma

Adrenocortical carcinoma (ACC) is a rare malignancy of the adrenal cortex, associated with a generally dismal prognosis owing to its aggressive behavior. Here are the latest discoveries pertaining to this disease.

Apoptotic Caspases

Apoptotic caspases belong to the protease enzyme family and are known to play an essential role in inflammation and programmed cell death. Here is the latest research.

Cancer Biology: Molecular Imaging

Molecular imaging enables noninvasive imaging of key molecules that are crucial to tumor biology. Discover the latest research in molecular imaging in cancer biology in this feed.

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

Antibody-Dependent Cell Cytotoxicity

Antibody-dependent cellular toxicity refers to the lysis of a target cell by a non-sensitized effector cell of the immune system as a result of antibodies binding to the target cell membrane and engaging the Fc receptors on the immune effector cells. Find the latest research on antibody-dependent cellular toxicity here.