Cell Cycle And Cancer PdfBy Damocles O. In and pdf 07.04.2021 at 11:58 3 min read
File Name: cell cycle and cancer .zip
The cell cycle , or cell-division cycle , is the series of events that take place in a cell that cause it to divide into two daughter cells. These events include the duplication of its DNA DNA replication and some of its organelles , and subsequently the partitioning of its cytoplasm and other components into two daughter cells in a process called cell division. In cells with nuclei eukaryotes , i.
This interactive module explores the phases, checkpoints, and protein regulators of the cell cycle. The module also shows how mutations in genes that encode cell cycle regulators can lead to the development of cancer. Students can toggle between two different views of the cell cycle by pressing the text in the center of the graphic. This view is appropriate for all levels of high school biology. Not all downloadable documents for the resource may be available in this format.
Cell Cycle in Cancer
In transgenic mice, overexpression of several of these cell cycle proteins induces or contributes to tumorigenesis, revealing their prominent oncogenic roles.
Importantly, in some cases the continued presence of a cell cycle protein has also been shown to be required for tumour maintenance and progression, for example, for cyclin D1, cyclin D3 and CDK4, thereby providing a clear rationale for targeting these proteins in cancer treatment. Kinases involved in cell cycle checkpoint function such as CHK1 and WEE1 also constitute potential therapeutic targets. Their inhibition compromises checkpoint function, causes excessive DNA damage and eventually leads to apoptosis, particularly in cells with compromised p53 function.
Compounds targeting Aurora A, particularly alisertib, have been extensively studied in preclinical models and demonstrated synergy with many other targeted therapies, leading to tumour regression in various cancer models. Moreover, clinical studies revealed encouraging activity of alisertib in peripheral T cell lymphoma, non-Hodgkin lymphoma, non-small-cell lung cancer and breast cancer. Cancer is characterized by uncontrolled tumour cell proliferation resulting from aberrant activity of various cell cycle proteins.
Therefore, cell cycle regulators are considered attractive targets in cancer therapy. Intriguingly, animal models demonstrate that some of these proteins are not essential for proliferation of non-transformed cells and development of most tissues.
By contrast, many cancers are uniquely dependent on these proteins and hence are selectively sensitive to their inhibition. After decades of research on the physiological functions of cell cycle proteins and their relevance for cancer, this knowledge recently translated into the first approved cancer therapeutic targeting of a direct regulator of the cell cycle. In this Review, we focus on proteins that directly regulate cell cycle progression such as cyclin-dependent kinases CDKs , as well as checkpoint kinases, Aurora kinases and Polo-like kinases PLKs.
We discuss the role of cell cycle proteins in cancer, the rationale for targeting them in cancer treatment and results of clinical trials, as well as the future therapeutic potential of various cell cycle inhibitors. Anders, L. Cancer Cell 20 , — Malumbres, M. Cell cycle, CDKs and cancer: a changing paradigm. Cancer 9 , — Kollmann, K. A new kinase-independent function of CDK6 links the cell cycle to tumor angiogenesis. Cancer Cell 24 , — To cycle or not to cycle: a critical decision in cancer.
Cancer 1 , — Sherr, C. Living with or without cyclins and cyclin-dependent kinases. Genes Dev. Hydbring, P. Non-canonical functions of cell cycle cyclins and cyclin-dependent kinases. Cell Biol. Beroukhim, R. The landscape of somatic copy-number alteration across human cancers.
Nature , — Schmidt, E. Cancer Res. Science , — Corcoran, M. Dysregulation of cyclin dependent kinase 6 expression in splenic marginal zone lymphoma through chromosome 7q translocations. Oncogene 18 , — Sotillo, R.
Wide spectrum of tumors in knock-in mice carrying a Cdk4 protein insensitive to INK4 inhibitors. EMBO J. Invasive melanoma in Cdk4-targeted mice. Natl Acad.
USA 98 , — Wang, T. Rojas, P. Cyclin D2 and cyclin D3 play opposite roles in mouse skin carcinogenesis. Oncogene 26 , — Wang, X.
Unexpected reduction of skin tumorigenesis on expression of cyclin-dependent kinase 6 in mouse epidermis. Yamamoto, H. Enhanced skin carcinogenesis in cyclin D1-conditional transgenic mice: cyclin D1 alters keratinocyte response to calcium-induced terminal differentiation. Miliani de Marval, P. Enhanced malignant tumorigenesis in Cdk4 transgenic mice. Oncogene 23 , — Yu, Q.
Specific protection against breast cancers by cyclin D1 ablation. The first study to demonstrate the oncogene-dependent requirement for cyclin D1 in mammary tumorigenesis in vivo using mouse cancer models. Bowe, D. Suppression of Neu -induced mammary tumor growth in cyclin D1 deficient mice is compensated for by cyclin E. Oncogene 21 , — Requirement for CDK4 kinase function in breast cancer. Cancer Cell 9 , 23—32 Reddy, H. Cyclin-dependent kinase 4 expression is essential for neu-induced breast tumorigenesis.
Landis, M. Cyclin D1-dependent kinase activity in murine development and mammary tumorigenesis. Cancer Cell 9 , 13—22 References 20—22 demonstrated the requirement for CDK4 kinase activity in mammary tumorigenesis using mouse cancer models, indicating the potential value of inhibiting CDK4 in breast cancer therapy. Sicinska, E. Requirement for cyclin D3 in lymphocyte development and T cell leukemias. Cancer Cell 4 , — Hu, M. A requirement for cyclin-dependent kinase 6 in thymocyte development and tumorigenesis.
This work showed that mice lacking CDK6 are resistant to lymphoma formation induced by v-AKT and therefore suggested that CDK6-selective inhibitors may be used to treat lymphoid malignancies. Puyol, M. A synthetic lethal interaction between K-Ras oncogenes and Cdk4 unveils a therapeutic strategy for non-small cell lung carcinoma.
Cancer Cell 18 , 63—73 Choi, Y. The requirement for cyclin D function in tumor maintenance. Cancer Cell 22 , — Sawai, C. Watanabe, N. Ma, T. Okuda, M. Cell , — Strohmaier, H. Human F-box protein hCdc4 targets cyclin E for proteolysis and is mutated in a breast cancer cell line. Koepp, D. Scaltriti, M. USA , — Etemadmoghadam, D. Spruck, C. Kemp, Z.
CDC4 mutations occur in a subset of colorectal cancers but are not predicted to cause loss of function and are not associated with chromosomal instability.
Cancer and the cell cycle
The cell cycle coordinates core functions such as replication and cell division. However, cell-cycle-regulated transcription in the control of non-core functions, such as cell identity maintenance through specific transcription factors TFs and signalling pathways remains unclear. Here, we provide a resource consisting of mapped transcriptomes in unsynchronized HeLa and U2OS cancer cells sorted for cell cycle phase by Fucci reporter expression. We developed a novel algorithm for data analysis that enables efficient visualization and data comparisons and identified cell cycle synchronization of Notch signalling and TFs associated with development. Furthermore, the cell cycle synchronizes with the circadian clock, providing a possible link between developmental transcriptional networks and the cell cycle. In conclusion we find that cell cycle synchronized transcriptional patterns are temporally compartmentalized and more complex than previously anticipated, involving genes, which control cell identity and development.
Abstract Deregulation of the cell cycle underlies the aberrant cell proliferation that characterizes cancer and loss of cell cycle checkpoint control promotes PDF. Sections. Abstract; Introduction; The cell cycle machinery—a.
The cell cycle, the process by which cells progress and divide, lies at the heart of cancer. In normal cells, the cell cycle is controlled by a complex series of signaling pathways by which a cell grows, replicates its DNA and divides. This process also includes mechanisms to ensure errors are corrected, and if not, the cells commit suicide apoptosis.
This activity guides the analysis of a published scientific figure from a study that investigated how random mutations during cell division can contribute to cancer. Hereditary and environmental factors explain only a fraction of overall cancer risk. In this study, researchers investigated how a third factor, chance mutations during stem cell division and DNA replication, may contribute to the cancer rates of various body tissues. The figure compares how many times stem cells divide in different tissues with the lifetime risks of developing cancer in those tissues. Not all downloadable documents for the resource may be available in this format.
Metrics details. Major currently used anticancer therapeutics either directly damage DNA or target and upset basic cell division mechanisms like DNA replication and chromosome segregation. These insults elicit activation of cell cycle checkpoints, safeguard mechanisms that cells implement to correctly complete cell cycle phases, repair damage or eventually commit suicide in case damage is unrepairable.
Paclitaxel Taxol and carboplatin induce differential cell-cycle profiles in cell lines of head and neck squamous cell carcinoma.
Cell cycle , the ordered sequence of events that occur in a cell in preparation for cell division. The cell cycle is a four-stage process in which the cell increases in size gap 1, or G1, stage , copies its DNA synthesis, or S, stage , prepares to divide gap 2, or G2, stage , and divides mitosis , or M, stage. The stages G1, S, and G2 make up interphase, which accounts for the span between cell divisions. The proteins that play a role in stimulating cell division can be classified into four groups— growth factors , growth factor receptors , signal transducers, and nuclear regulatory proteins transcription factors.