miR-143 or miR-145 overexpression increases cetuximab-mediated antibody-dependent cellular cytotoxicity in human colon cancer cells

Oncotarget
Sofia E GomesPedro M Borralho

Abstract

miR-143 and miR-145 are downregulated in colon cancer. Here, we tested the effect of restoring these miRNAs on sensitization to cetuximab in mutant KRAS (HCT116 and SW480) and wild-type KRAS (SW48) colon cancer cells. We evaluated cetuximab-mediated antibody-dependent cellular cytotoxicity (ADCC) and the modulation of signaling pathways involved in immune effector cell-mediated elimination of cancer cells. Stable miR-143 or miR-145 overexpression increased cell sensitivity to cetuximab, resulting in a significant increase of cetuximab-mediated ADCC independently of KRAS status. Importantly, HCT116 cells overexpressing these miRNAs triggered apoptosis in result of cetuximab-mediated ADCC, effected by peripheral blood mononuclear cells (p < 0.01). This was associated with increased apoptosis and caspase-3/7 activity, and reduced Bcl-2 protein expression (p < 0.01). In addition, caspase inhibition abrogated cetuximab-mediated ADCC in HCT116 cells overexpressing either miR-143 or miR-145 (p < 0.01). Furthermore, Bcl-2 silencing led to high level of cetuximab-mediated ADCC, compared to control siRNA (p < 0.05). Importantly, granzyme B inhibition, abrogated cetuximab-mediated ADCC, reducing caspase-3/7 activity (p < 0.01). Collective...Continue Reading

References

Dec 1, 1981·The American Journal of Medicine·D L DexterP Calabresi
Jan 5, 1999·The Journal of Experimental Medicine·G MacDonaldA H Greenberg
Mar 31, 2000·Nature Medicine·R A ClynesJ V Ravetch
Jul 4, 2001·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·F RobertH W Waksal
Oct 3, 2002·Nature Reviews. Immunology·Joseph A Trapani, Mark J Smyth
May 20, 2003·Immunological Reviews·Sarah J LordR Chris Bleackley
Dec 21, 2004·Molecular Immunology·Valentina ScrepantiHans-Gustaf Ljunggren
Aug 17, 2005·Cancer Research·Marilena V IorioCarlo M Croce
Nov 11, 2005·Breast Cancer Research : BCR·Manabu EmiTetsuya Toge
Feb 8, 2006·Proceedings of the National Academy of Sciences of the United States of America·Stefano VoliniaCarlo M Croce
Oct 25, 2006·Nature Reviews. Cancer·George A Calin, Carlo M Croce
Nov 23, 2006·Assay and Drug Development Technologies·Joakim Glamann, Anker Jon Hansen
May 29, 2007·Oncogene·K TakedaM J Smyth
Aug 21, 2007·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Wu ZhangHeinz-Josef Lenz
Aug 5, 2008·Critical Reviews in Oncology/hematology·Bruno VincenziGiuseppe Tonini
Aug 8, 2008·Bioinformation·Jayapal ManikandanPeter Natesan Pushparaj
Dec 5, 2008·Scandinavian Journal of Urology and Nephrology. Supplementum·Antonio Lopez-Beltran
Jan 13, 2009·Oncogene·X ChenC-Y Zhang
Jan 24, 2009·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Frédéric BibeauFlorence Boissière-Michot
Feb 26, 2009·Cell·Richard W Carthew, Erik J Sontheimer
May 15, 2009·Oncology·Takeshi TakagiYukihiro Akao
Jun 19, 2009·Nature Reviews. Cancer·Axel WaltherDavid Kerr
Sep 22, 2009·Dental Materials : Official Publication of the Academy of Dental Materials·Ebru UrcanFranz Xaver Reichl
Sep 23, 2009·Laboratory Investigation; a Journal of Technical Methods and Pathology·Wendy Anne BoivinDavid James Granville
Jan 19, 2010·Nucleic Acids Research·Sang Woo KimBino John
Jan 23, 2010·Cancer Gene Therapy·Y AkaoT Naoe
Jan 27, 2010·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Alberto Bardelli, Salvatore Siena
May 31, 2011·Molecular Cancer Therapeutics·Dipankar PramanikAnirban Maitra
Jun 3, 2011·Gene Therapy·A G BaderP Lammers

❮ Previous
Next ❯

Citations

Aug 12, 2017·International Journal of Molecular Sciences·Hye-Jin ParkMinjung Song
Jul 18, 2017·International Journal of Molecular Sciences·Ingrid GarajováGiovanni Brandi
Aug 30, 2018·International Journal of Cancer. Journal International Du Cancer·Neha NandaDevinder Kumar Dhawan
Feb 23, 2020·Cancer Science·Yoshihisa TokumaruYukihiro Akao
Apr 23, 2016·Oncotarget·Nobuo TsuchidaMichele Grieco
Jan 18, 2017·Biological Chemistry·Yang Zhang, Jing Wang
Oct 16, 2019·Frontiers in Oncology·Roberta RoncaratiMassimo Negrini
Jan 2, 2019·International Journal of Molecular Sciences·Haochen ZhaoLei Wang
May 2, 2019·BMC Molecular and Cell Biology·Chun YangShao Ping Deng
Sep 19, 2019·Cancers·Yoojung KwonDooil Jeoung
Sep 20, 2018·International Journal of Molecular Sciences·Lei DingQinghua Cui

❮ Previous
Next ❯

Methods Mentioned

BETA
flow cytometry
fluorescence microscopy
xenograft
transfections
Assay
protein assay
electrophoresis

Software Mentioned

xCELLigence
RTCA
IM50
Image Lab
InCyte
Leica
Image J

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.

BCL-2 Family Proteins

BLC-2 family proteins are a group that share the same homologous BH domain. They play many different roles including pro-survival signals, mitochondria-mediated apoptosis and removal or damaged cells. They are often regulated by phosphorylation, affecting their catalytic activity. Here is the latest research on BCL-2 family proteins.

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

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.