Abstract:
:Data accumulating during the last two decades suggest that tumorigenesis is held in check by two major intrinsic failsafe mechanisms; apoptosis and cellular senescence. While apoptosis is a programmed cell death process, cellular senescence, which is the focus of this article, is defined as irreversible cell cycle arrest. This process is triggered either by telomere erosion or by acute stress signals including oncogenic stress induced by overactive oncogenes or underactive tumor suppressor genes. The outcome of this is often replication overload and oxidative stress resulting in DNA damage. Oncogenic stress induces at least three intrinsic pathways, p16/pRb-, Arf/p53/p21- and the DNA damage response (DDR)-pathways, that induce premature senescence if the stress exceeds a threshold level. Oncogene-induced senescence (OIS) is frequently observed in premalignant lesions both in animal tumor models and in human patients but is essentially absent in advanced cancers, suggesting that malignant tumor cells have found ways to bypass or escape senescence. This review focuses on cell-autonomous mechanism by which certain oncogenes, tumor suppressor genes and components of the DDR/DNA-repair machinery suppress senescence - mechanisms that are exploited by tumor cells to evade senescence and continue to multiply. In this way, tumor cells become addicted to the continuous activity of senescence suppressor proteins. However, some senescence pathways, although under suppression, may remain intact and can be re-established if senescence suppressor proteins are inactivated or if senescence inducers are reactivated. This can hopefully form the basis for a "pro-senescence therapy" strategy to combat cancer in the future.
journal_name
Semin Cancer Bioljournal_title
Seminars in cancer biologyauthors
Larsson LGdoi
10.1016/j.semcancer.2011.10.005subject
Has Abstractpub_date
2011-12-01 00:00:00pages
367-76issue
6eissn
1044-579Xissn
1096-3650pii
S1044-579X(11)00079-4journal_volume
21pub_type
杂志文章,评审abstract::Small molecule inhibitors target specific metabolic pathways in tumor cells and are a promising class of drugs for the treatment of cancers. The best known example is the treatment of chronic myeloid leukemia (CML) with Gleevec. This is a small molecule inhibitor of the Bcr-Abl kinase which has been shown to drive the...
journal_title:Seminars in cancer biology
pub_type: 杂志文章,评审
doi:10.1016/j.semcancer.2005.07.002
更新日期:2005-12-01 00:00:00
abstract::Investigations across a range of disciplines over the past decade have brought the study of cell motility and its role in invasion to an exciting threshold. The biophysical forces proximally involved in generating cell locomotion, as well as the underlying signaling and genomic regulatory processes, are gradually beco...
journal_title:Seminars in cancer biology
pub_type: 杂志文章,评审
doi:10.1006/scbi.2000.0362
更新日期:2001-04-01 00:00:00
abstract::Epidemiological studies implicate steroid hormones as important factors in the development of neoplasia, and hormonal manipulation constitutes an important treatment arm in cancer therapy. Recent studies demonstrate a key role for nuclear receptor proteins in the expression of genes encoding the cytochrome P450 enzyme...
journal_title:Seminars in cancer biology
pub_type: 杂志文章,评审
doi:
更新日期:1994-10-01 00:00:00
abstract::DNA damaging agents (ionizing radiation and chemotherapeutics) are considered as most effective in cancer treatment. However, there is a subpopulation of carcinoma cells within the tumour demonstrating resistance to DNA damaging treatment approaches. It is suggested that limited tumour response to this kind of therapy...
journal_title:Seminars in cancer biology
pub_type: 杂志文章,评审
doi:10.1016/j.semcancer.2014.06.002
更新日期:2015-04-01 00:00:00
abstract::In this short review, we will give an overview of the various genes that can be activated by insertion of proviral DNA of the mouse mammary tumor virus during the formation of mammary cancer. These genes fall within three families: Wnt genes, FGF genes and Notch-related genes. We will summarize our current understandi...
journal_title:Seminars in cancer biology
pub_type: 杂志文章,评审
doi:10.1006/scbi.1995.0018
更新日期:1995-06-01 00:00:00
abstract::Notch signaling is mediated by cell-cell interactions and is critical for cell fate determination in many species. Recently, a family of mastermind-like (MAML) transcriptional co-activator genes was identified that encode proteins that cooperate with Notch and CSL to activate transcription. Here, we review our current...
journal_title:Seminars in cancer biology
pub_type: 杂志文章
doi:10.1016/j.semcancer.2004.04.014
更新日期:2004-10-01 00:00:00
abstract::Alterations in the rate and pattern of cell movement are prominent features of many human diseases, including inflammation, cardiovascular disease and cancer. The ability to regulate the interactions of cells with each other and with adhesion factors in extracellular matrices therefore offers a novel approach to the t...
journal_title:Seminars in cancer biology
pub_type: 杂志文章,评审
doi:
更新日期:1993-10-01 00:00:00
abstract::The processes of intraepithelial migration, intraluminal seeding, and field cancerization as models for initiation, spread, and recurrences of urothelial cell carcinoma (UCC) are reviewed in light of recent molecular investigations. The accumulated molecular data on synchronous and metachronous tumors indicate that th...
journal_title:Seminars in cancer biology
pub_type: 杂志文章,评审
doi:10.1016/j.semcancer.2006.02.002
更新日期:2007-06-01 00:00:00
abstract::While the centrality of aberrant cell proliferation in cancer was widely acknowledged long ago, it is only recently that the control of cell death has been recognized as an important target in carcinogenesis. Various lines of evidence now suggest that p53 is a positive regulator of cell death, and particularly of apop...
journal_title:Seminars in cancer biology
pub_type: 杂志文章,评审
doi:
更新日期:1994-06-01 00:00:00
abstract::The key molecule for normal B cells is the surface Ig (sIg) of the B-cell receptor, which influences cell behaviour, even after neoplastic transformation. During B-cell maturation, sIg accumulates somatic mutations in the Ig variable region (V) genes and tumours retain these patterns, thereby revealing the point of di...
journal_title:Seminars in cancer biology
pub_type: 杂志文章,评审
doi:10.1016/j.semcancer.2010.08.004
更新日期:2010-12-01 00:00:00
abstract::Prostate cancer (PCa), a hormonally-driven cancer, ranks first in incidence and second in cancer related mortality in men in most Western industrialized countries. Androgen and androgen receptor (AR) are the dominant modulators of PCa growth. Over the last two decades multiple advancements in screening, treatment, sur...
journal_title:Seminars in cancer biology
pub_type: 杂志文章,评审
doi:10.1016/j.semcancer.2016.06.003
更新日期:2016-10-01 00:00:00
abstract::Cancer cells are exposed to adverse conditions within the tumor microenvironment that challenge cells to adapt and survive. Several of these homeostatic perturbations insults alter the normal function of the endoplasmic reticulum (ER), resulting in the accumulation of misfolded proteins. ER stress triggers a conserved...
journal_title:Seminars in cancer biology
pub_type: 杂志文章,评审
doi:10.1016/j.semcancer.2018.01.011
更新日期:2018-06-01 00:00:00
abstract::Abnormally activated RAS proteins are the main oncogenic driver that governs the functioning of major signaling pathways involved in the initiation and development of human malignancies. Mutations in RAS genes and or its regulators, most frequent in human cancers, are the main force for incessant RAS activation and as...
journal_title:Seminars in cancer biology
pub_type: 杂志文章,评审
doi:10.1016/j.semcancer.2018.03.001
更新日期:2019-02-01 00:00:00
abstract::The global burden of breast cancer (BC) is increasing significantly. This trend is caused by several factors such as late diagnosis, limited treatment options for certain BC subtypes, drug resistance which all lead to poor clinical outcomes. Recent research has reported the role of epigenetic alterations in the mechan...
journal_title:Seminars in cancer biology
pub_type: 杂志文章
doi:10.1016/j.semcancer.2020.08.009
更新日期:2020-08-25 00:00:00
abstract::Colorectal cancer is highly incident worldwide and presents a health burden with elevated mortality rate despite prevention, detection, and treatment, mainly due to metastatic liver disease. Histological growth patterns of colorectal cancer liver metastases have emerged as a reproducible prognostic factor, with biolog...
journal_title:Seminars in cancer biology
pub_type: 杂志文章
doi:10.1016/j.semcancer.2020.07.007
更新日期:2020-07-14 00:00:00
abstract::Angiogenesis plays a pivotal role in cancer progression and is required for tissue invasion and metastasis. Starting with Folkman's initial observations in 1971, basic research continued to shed new molecular insight into this multifaceted process, leading to the development of several anti-angiogenic drugs. To date, ...
journal_title:Seminars in cancer biology
pub_type: 杂志文章,评审
doi:10.1016/j.semcancer.2017.11.005
更新日期:2019-06-01 00:00:00
abstract::SINE-VNTR-Alus (SVA) are non-autonomous hominid specific retrotransposons that are associated with disease in humans. SVAs are evolutionarily young and presumably mobilized by the LINE-1 reverse transcriptase in trans. SVAs are currently active and may impact the host through a variety of mechanisms including insertio...
journal_title:Seminars in cancer biology
pub_type: 杂志文章,评审
doi:10.1016/j.semcancer.2010.04.001
更新日期:2010-08-01 00:00:00
abstract::Among unusual models to study cell death mechanisms, the protist Dictyostelium is remarkable because of its strategic phylogenetic position, with early emergence among eukaryotes and unicellular/multicellular transition, and its very favorable experimental and genetic flexibility. Dictyostelium shows developmental vac...
journal_title:Seminars in cancer biology
pub_type: 杂志文章,评审
doi:10.1016/j.semcancer.2006.10.010
更新日期:2007-04-01 00:00:00
abstract::Gynaecological carcinosarcomas are the most lethal gynaecological malignancies that are often highly resistant to standard chemotherapy. They are composed of both carcinomatous and sarcomatous components and are associated with high rates of metastatic disease. Due to their rarity, molecular studies have been carried ...
journal_title:Seminars in cancer biology
pub_type: 杂志文章,评审
doi:10.1016/j.semcancer.2019.10.006
更新日期:2020-04-01 00:00:00
abstract::Utilization of thermal therapy (hyperthermia) is defined as the application of exogenous heat induction and represents a concept that is far from new as it goes back to ancient times when heat was used for treating various diseases, including malignancies. Such therapeutic strategy has gained even more popularity (ove...
journal_title:Seminars in cancer biology
pub_type: 杂志文章,评审
doi:10.1016/j.semcancer.2016.03.004
更新日期:2016-06-01 00:00:00
abstract::Oral squamous cell carcinomas (OSCC) are a heterogeneous group of cancers arising from the mucosal lining of the oral cavity. A majority of these cancers are associated with lifestyle risk habits including smoking, excessive alcohol consumption and betel quid chewing. Cetuximab, targeting the epidermal growth factor r...
journal_title:Seminars in cancer biology
pub_type: 杂志文章,评审
doi:10.1016/j.semcancer.2019.09.011
更新日期:2020-04-01 00:00:00
abstract::The biology and the pathology of the stress-activated protein kinases (SAPKs; p38s and c-Jun-NH(2)-terminal kinases (JNKs)) are somewhat confusing. In some systems, these enzymes augment cell proliferation whereas in other cells they support growth arrest and tumor suppressing activity. Similarly, in some types of can...
journal_title:Seminars in cancer biology
pub_type: 杂志文章,评审
doi:10.1016/j.semcancer.2004.04.006
更新日期:2004-08-01 00:00:00
abstract::Viability is a fundamental determinant of all cellular functions, and regulation of cell viability is important in shaping tissue differentiation and organism development. The genes in the bcl-2 family can profoundly influence cell viability. In addition to bcl-2, cellular genes in this family include bcl-x, bax, mcl-...
journal_title:Seminars in cancer biology
pub_type: 杂志文章,评审
doi:10.1006/scbi.1995.0005
更新日期:1995-02-01 00:00:00
abstract::Cells adhere to one another and/or to matrices that surround them. Regulation of cell-cell (intercellular) and cell-matrix adhesion is tightly controlled in normal cells, however, defects in cell adhesion are common in the majority of human cancers. Multilateral communication among tumor cells with the extracellular m...
journal_title:Seminars in cancer biology
pub_type: 杂志文章,评审
doi:10.1016/j.semcancer.2010.05.002
更新日期:2010-06-01 00:00:00
abstract::Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths worldwide. Similar to many other malignancies, CRC is a heterogeneous disease, making it a clinical challenge for optimization of treatment modalities in reducing the morbidity and mortality associated with this disease. A more precise under...
journal_title:Seminars in cancer biology
pub_type: 杂志文章,评审
doi:10.1016/j.semcancer.2018.05.002
更新日期:2019-04-01 00:00:00
abstract::Maintenance and accurate propagation of the genetic material are key features for physiological development and wellbeing. The replication licensing machinery is crucial for replication precision as it ensures that replication takes place once per cell cycle. Thus, the expression status of the components comprising th...
journal_title:Seminars in cancer biology
pub_type: 杂志文章,评审
doi:10.1016/j.semcancer.2015.12.002
更新日期:2016-06-01 00:00:00
abstract::People are continuously exposed exogenously to varying amounts of chemicals that have been shown to have carcinogenic or mutagenic properties in experimental systems. Exposure can occur exogenously when these agents are present in food, air or water, and also endogenously when they are products of metabolism or pathop...
journal_title:Seminars in cancer biology
pub_type: 杂志文章,评审
doi:10.1016/j.semcancer.2004.06.010
更新日期:2004-12-01 00:00:00
abstract::We have found that not all Epstein-Barr viral (EBV) plasmids are duplicated each cell cycle. This inefficiency is intrinsic to EBV's mechanism of DNA synthesis in latently infected cells and necessarily leads to a loss of EBV plasmids from proliferating cells. If EBV provides its host cells advantages that allow those...
journal_title:Seminars in cancer biology
pub_type: 杂志文章,评审
doi:10.1016/j.semcancer.2009.07.006
更新日期:2009-12-01 00:00:00
abstract::In vitro transformation of replicating myogenic cells by a variety of oncogenes is always accompanied by inhibition of the transition to the terminally differentiated state. Three main levels of interference by oncogenes may ultimately prevent transcription of skeletal muscle-specific genes. First, the transcription o...
journal_title:Seminars in cancer biology
pub_type: 杂志文章
doi:
更新日期:1994-04-01 00:00:00
abstract::Primary liver cancer is the second most common malignancy, and currently results in 360,000 incident cases, and 350,000 deaths a year in China. For the past four decades, three national surveys on cancer mortality during the periods of 1973-1975, 1990-1992, and 2004-2005 have made it possible to estimate China's past ...
journal_title:Seminars in cancer biology
pub_type: 杂志文章,评审
doi:10.1016/j.semcancer.2010.11.002
更新日期:2011-02-01 00:00:00