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      KLF4 transcription factor in tumorigenesis

      review-article
      Author(s): 1 , 2 , 3 , 1 , 2 ,
      Publication date (Electronic):
      Journal: Cell Death Discovery
      Publisher: Nature Publishing Group UK
      Keywords: Oncogenesis, Pancreatic cancer

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          Abstract

          Krüppel-like transcriptional factor is important in maintaining cellular functions. Deletion of Krüppel-like transcriptional factor usually causes abnormal embryonic development and even embryonic death. KLF4 is a prominent member of this family, and embryonic deletion of KLF4 leads to alterations in skin permeability and postnatal death. In addition to its important role in embryo development, it also plays a critical role in inflammation and malignancy. It has been investigated that KLF4 has a regulatory role in a variety of cancers, including lung, breast, prostate, colorectal, pancreatic, hepatocellular, ovarian, esophageal, bladder and brain cancer. However, the role of KLF4 in tumorigenesis is complex, which may link to its unique structure with both transcriptional activation and transcriptional repression domains, and to the regulation of its upstream and downstream signaling molecules. In this review, we will summarize the structural and functional aspects of KLF4, with a focus on KLF4 as a clinical biomarker and therapeutic target in different types of tumors.

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          Cancer Statistics, 2021

          Rebecca Siegel, Kimberly D Miller, Hannah Fuchs … (2021)
          Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths in the United States and compiles the most recent data on population-based cancer occurrence. Incidence data (through 2017) were collected by the Surveillance, Epidemiology, and End Results Program; the National Program of Cancer Registries; and the North American Association of Central Cancer Registries. Mortality data (through 2018) were collected by the National Center for Health Statistics. In 2021, 1,898,160 new cancer cases and 608,570 cancer deaths are projected to occur in the United States. After increasing for most of the 20th century, the cancer death rate has fallen continuously from its peak in 1991 through 2018, for a total decline of 31%, because of reductions in smoking and improvements in early detection and treatment. This translates to 3.2 million fewer cancer deaths than would have occurred if peak rates had persisted. Long-term declines in mortality for the 4 leading cancers have halted for prostate cancer and slowed for breast and colorectal cancers, but accelerated for lung cancer, which accounted for almost one-half of the total mortality decline from 2014 to 2018. The pace of the annual decline in lung cancer mortality doubled from 3.1% during 2009 through 2013 to 5.5% during 2014 through 2018 in men, from 1.8% to 4.4% in women, and from 2.4% to 5% overall. This trend coincides with steady declines in incidence (2.2%-2.3%) but rapid gains in survival specifically for nonsmall cell lung cancer (NSCLC). For example, NSCLC 2-year relative survival increased from 34% for persons diagnosed during 2009 through 2010 to 42% during 2015 through 2016, including absolute increases of 5% to 6% for every stage of diagnosis; survival for small cell lung cancer remained at 14% to 15%. Improved treatment accelerated progress against lung cancer and drove a record drop in overall cancer mortality, despite slowing momentum for other common cancers.
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            Ovarian cancer statistics, 2018

            Lindsey A Torre, Britton Trabert, Carol DeSantis … (2018)
            In 2018, there will be approximately 22,240 new cases of ovarian cancer diagnosed and 14,070 ovarian cancer deaths in the United States. Herein, the American Cancer Society provides an overview of ovarian cancer occurrence based on incidence data from nationwide population-based cancer registries and mortality data from the National Center for Health Statistics. The status of early detection strategies is also reviewed. In the United States, the overall ovarian cancer incidence rate declined from 1985 (16.6 per 100,000) to 2014 (11.8 per 100,000) by 29% and the mortality rate declined between 1976 (10.0 per 100,000) and 2015 (6.7 per 100,000) by 33%. Ovarian cancer encompasses a heterogenous group of malignancies that vary in etiology, molecular biology, and numerous other characteristics. Ninety percent of ovarian cancers are epithelial, the most common being serous carcinoma, for which incidence is highest in non-Hispanic whites (NHWs) (5.2 per 100,000) and lowest in non-Hispanic blacks (NHBs) and Asians/Pacific Islanders (APIs) (3.4 per 100,000). Notably, however, APIs have the highest incidence of endometrioid and clear cell carcinomas, which occur at younger ages and help explain comparable epithelial cancer incidence for APIs and NHWs younger than 55 years. Most serous carcinomas are diagnosed at stage III (51%) or IV (29%), for which the 5-year cause-specific survival for patients diagnosed during 2007 through 2013 was 42% and 26%, respectively. For all stages of epithelial cancer combined, 5-year survival is highest in APIs (57%) and lowest in NHBs (35%), who have the lowest survival for almost every stage of diagnosis across cancer subtypes. Moreover, survival has plateaued in NHBs for decades despite increasing in NHWs, from 40% for cases diagnosed during 1992 through 1994 to 47% during 2007 through 2013. Progress in reducing ovarian cancer incidence and mortality can be accelerated by reducing racial disparities and furthering knowledge of etiology and tumorigenesis to facilitate strategies for prevention and early detection. CA Cancer J Clin 2018;68:284-296. © 2018 American Cancer Society.
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              Exosomes

              D Pegtel, Stephen Gould (2019)
              Exosomes are small, single-membrane, secreted organelles of ∼30 to ∼200 nm in diameter that have the same topology as the cell and are enriched in selected proteins, lipids, nucleic acids, and glycoconjugates. Exosomes contain an array of membrane-associated, high-order oligomeric protein complexes, display pronounced molecular heterogeneity, and are created by budding at both plasma and endosome membranes. Exosome biogenesis is a mechanism of protein quality control, and once released, exosomes have activities as diverse as remodeling the extracellular matrix and transmitting signals and molecules to other cells. This pathway of intercellular vesicle traffic plays important roles in many aspects of human health and disease, including development, immunity, tissue homeostasis, cancer, and neurodegenerative diseases. In addition, viruses co-opt exosome biogenesis pathways both for assembling infectious particles and for establishing host permissiveness. On the basis of these and other properties, exosomes are being developed as therapeutic agents in multiple disease models.
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                Author and article information

                Contributors
                Keping Xie:
                ORCID: http://orcid.org/0000-0001-7887-9586
                scutmedicine@scut.edu.cn
                Journal
                Journal ID (nlm-ta): Cell Death Discov
                Journal ID (iso-abbrev): Cell Death Discov
                Title: Cell Death Discovery
                Publisher: Nature Publishing Group UK (London )
                ISSN (Electronic): 2058-7716
                Publication date (Electronic): 8 April 2023
                Publication date PMC-release: 8 April 2023
                Publication date Collection: 2023
                Volume: 9
                Electronic Location Identifier: 118
                Affiliations
                [1 ]GRID grid.79703.3a, ISNI 0000 0004 1764 3838, Center for Pancreatic Cancer Research, , The South China University of Technology School of Medicine, ; Guangzhou, China
                [2 ]GRID grid.79703.3a, ISNI 0000 0004 1764 3838, The South China University of Technology Comprehensive Cancer Center, ; Guangdong, China
                [3 ]GRID grid.79703.3a, ISNI 0000 0004 1764 3838, The Second Affiliated Hospital and Guangzhou First People’s Hospital, , South China University of Technology School of Medicine, ; Guangdong, China
                Author information
                http://orcid.org/0000-0001-7887-9586
                Article
                Publisher ID: 1416
                DOI: 10.1038/s41420-023-01416-y
                PMC ID: 10082813
                PubMed ID: 37031197
                SO-VID: 8690eb20-78a9-41a5-8a16-1a5b778d8e08
                Copyright © © The Author(s) 2023
                License:

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                Date received : 18 February 2023
                Date revision received : 22 March 2023
                Date accepted : 24 March 2023
                Funding
                Funded by: FundRef https://doi.org/10.13039/501100001809, National Natural Science Foundation of China (National Science Foundation of China);
                Award ID: 82072632
                Award Recipient :
                Categories
                Subject: Review Article
                Custom metadata
                issue-copyright-statement © The Author(s) 2023

                Keywords: oncogenesis,pancreatic cancer
                Data availability:
                Keywords: oncogenesis, pancreatic cancer

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