Emerging Role of CREB in Epithelial to Mesenchymal Plasticity of Pancreatic Cancer
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive solid malignancy with a high rate of metastasis and therapeutic resistance as its major hallmarks. Although a defining mutational event in pancreatic cancer initiation is the presence of oncogenic KRAS , more advanced PDAC lesions accumulate a...
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Published in | Frontiers in oncology Vol. 12; p. 925687 |
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Main Authors | , , |
Format | Journal Article |
Language | English |
Published |
Frontiers Media S.A
21.06.2022
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Subjects | |
Online Access | Get full text |
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Summary: | Pancreatic ductal adenocarcinoma (PDAC) is an aggressive solid malignancy with a high rate of metastasis and therapeutic resistance as its major hallmarks. Although a defining mutational event in pancreatic cancer initiation is the presence of oncogenic
KRAS
, more advanced PDAC lesions accumulate additional genomic alterations, including loss of tumor suppressor gene
TP53.
Co-occurrence of mutant
KRAS
and
TP53
in PDAC promotes hyperactivation of cancer cell signaling pathways driving epithelial to mesenchymal plasticity (EMP). The cellular process of EMP influences the biological behavior of cancer cells by increasing their migratory and invasive properties, thus promoting metastasis. Our previous work has demonstrated that oncogenic KRAS-mediated activation of cyclic AMP response element-binding protein 1 (CREB) is one of the critical drivers of PDAC aggressiveness. The therapeutic approach of targeting this key transcription factor attenuates tumor burden in genetically engineered mouse models (GEMMs) of this disease. Herein, we discuss the significant role of CREB in perpetuating disease aggressiveness and therapeutic resistance through the EMP process. Furthermore, this review updates the therapeutic implications of targeting CREB, highlighting the challenges and emerging approaches in PDAC. |
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Bibliography: | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-3 content type line 23 ObjectType-Review-1 Reviewed by: Chethan Ashokkumar, University of Pittsburgh, United States; Manish Tripathi, The University of Texas Rio Grande Valley, United States Edited by: Aamir Ahmad, University of Alabama at Birmingham, United States This article was submitted to Molecular and Cellular Oncology, a section of the journal Frontiers in Oncology |
ISSN: | 2234-943X 2234-943X |
DOI: | 10.3389/fonc.2022.925687 |