Loss of the Cyclin-Dependent Kinase Inhibitor 1 in the Context of Brachyury-Mediated Phenotypic Plasticity Drives Tumor Resistance to Immune Attack

Frontiers in Oncology
Duane H HamiltonClaudia Palena

Abstract

The acquisition of mesenchymal features by carcinoma cells is now recognized as a driver of metastasis and tumor resistance to a range of anticancer therapeutics, including chemotherapy, radiation, and certain small-molecule targeted therapies. With the recent successful implementation of immunotherapies for the treatment of various types of cancer, there is growing interest in understanding whether an immunological approach could be effective at eradicating carcinoma cells bearing mesenchymal features. Recent studies, however, demonstrated that carcinoma cells that have acquired mesenchymal features may also exhibit decreased susceptibility to lysis mediated by immune effector cells, including antigen-specific CD8+ T cells, innate natural killer (NK), and lymphokine-activated killer (LAK) cells. Here, we investigated the mechanism involved in the immune resistance of carcinoma cells that express very high levels of the transcription factor brachyury, a molecule previously shown to drive the acquisition of mesenchymal features by carcinoma cells. Our results demonstrate that very high levels of brachyury expression drive the loss of the cyclin-dependent kinase inhibitor 1 (p21CIP1, p21), an event that results in decreased tumor...Continue Reading

References

Dec 1, 1996·The Journal of Cell Biology·L RaoE White
Apr 1, 1997·Genes & Development·J LaBaerE Harlow
Mar 26, 2004·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Kwong-Yok TsangJeffrey Schlom
May 25, 2004·Genes & Development·Sonia VegaM Angela Nieto
Apr 18, 2007·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Claudia PalenaJeffrey Schlom
Aug 12, 2009·Nature·Teruhisa KawamuraJuan Carlos Izpisúa Belmonte
Oct 28, 2009·Proceedings of the National Academy of Sciences of the United States of America·Manran LiuRichard G Pestell
Jan 15, 2010·The Journal of Clinical Investigation·Romaine I FernandoClaudia Palena
Jan 12, 2011·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Nerbil KilicUdo Schumacher
Mar 11, 2011·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·N V RajeshkumarManuel Hidalgo
Jul 30, 2011·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Kathleen A BridgesRaymond E Meyn
May 23, 2012·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Mario RoselliClaudia Palena
Sep 25, 2012·Nature·UNKNOWN Cancer Genome Atlas Network
Mar 5, 2013·Annals of Surgical Oncology·Akira HaroYoshihiko Maehara
Nov 28, 2013·Molecular and Cellular Biology·Xiao Ling LiAshish Lal
May 13, 2014·Journal of the National Cancer Institute·Claudia PalenaFiorella Guadagni
Jul 11, 2014·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Filipe PintoRui M Reis
Mar 4, 2015·Current Topics in Developmental Biology·Pierre Savagner
May 13, 2015·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Khanh DoShivaani Kummar
Jul 2, 2016·Cell·M Angela NietoJean Paul Thiery
Sep 2, 2016·Endocrine-related Cancer·Duane H HamiltonFiorella Guadagni
Jun 15, 2017·Molecular Oncology·Stéphane TerrySalem Chouaib
Sep 1, 2017·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Christopher R HeeryJames L Gulley

❮ Previous
Next ❯

Citations

Aug 14, 2018·Expert Opinion on Investigational Drugs·Siqing FuFunda Meric-Bernstein
Oct 13, 2019·Cancer Letters·Yuanyuan Jiang, Hanxiang Zhan
Mar 6, 2021·Immunology and Cell Biology·Amanda L PatchettA Bruce Lyons

❮ Previous
Next ❯

Methods Mentioned

BETA
xenograft
Protein Assay
immunoprecipitation
transfection
co-immunoprecipitation

Clinical Trials Mentioned

NCT00001846

Software Mentioned

Prism
GraphPad
Nexus Expression
GeneArt CRISPR Search and Design

Related Concepts

Related Feeds

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

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 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.

Cancer Vaccines

Cancer vaccines are vaccines that either treat existing cancer or prevent development of a cancer.