Cell Biology

Cell Biology

Question 1

Distinguish between the six original "hallmarks" of cancer

Sustaining proliferative signals, activating invasion and metastasis, resisting cell death, promoting angiogenesis, enabling replicative immortality, and avoiding growth suppressors were the six hallmarks at first (Hanahan & Weinberg, 2011).

Sustaining proliferative signals-Cancer cells can sustain proliferative signaling by producing factor ligands that respond via the expression of cognate receptors, stimulating the normal cells within the supporting tumor-associated stroma by the cancer cells(Hanahan & Weinberg, 2011). This elevates the cancer cells’ receptor proteins, causing hyperresponsiveness to the growth factor ligand.

Activating invasion and metastasis-The loss of cell to cell adhesion promotes the dissociation of malignant tumor cells from the primary tumor mass. At the same time, changes in cell-matrix differentiation enable the cells to invade the surrounding stroma.

Resisting cell death-Retinoblastoma (RB) and TP53 proteins regulate cell proliferation; activate senescence and apoptosis within the cells (Hanahan & Weinberg, 2011). Tumor cells can evade growth suppressors by causing defects in the RB pathways and TP53 proteins, leading to malfunction in the regulation of cell proliferation.

Enabling replicative immortality-Cell death by tumor cells is avoided by losing the TP53 proteins and increased production of antiapoptotic regulators (Bcl-2, Bcl-xL) or survival signals (Igf1/2). Upregulating the expression of the telomere promotes the telomeric DNA at adequate levels to avoid triggering cell death and senescence hence maintaining the replicative immortality of tumor cells (Hanahan & Weinberg, 2011).

Promoting angiogenesis-Angiogenesis supplies the tumor cells with nutrients and oxygen through sufficient blood circulation and ensures that waste products and carbon(IV)oxide are removed from the cells. Vascular endothelial growth factor, and angiogenesis inducer, are activated and maintained throughout the progression of the tumors to promote angiogenesis.

Avoiding growth suppressors- genetic mechanism such as chromosomal deletion, inactivation, and mutation or loss of upstream and downstream effectors allows tumor cells to evade growth suppressors.

Emerging hallmarks of cancer and enabling characteristics

The emerging hallmarks of cancer are reprogramming of energy metabolism. The tumor cells can alter their metabolism to match the energy requirements due to the continuous increased proliferation and growth—also avoiding immune destruction to avoid being eliminated by the body's defense system (Hanaha, 2022). The enabling characteristics Genome instability allows the mutations and chromosomal rearrangements to support neoplastic proliferation(Hanaha, 2022). In addition, tumor-promoting inflammation allows the tumor cells to evade destruction from the immune system, mainly the T and B lymphocytes, macrophages, and natural killer cells.

Using one hallmark (Enabling replicative immortality) as a therapeutic target

Chemotherapy agents can target the replicative immortality of the tumor cells. DNA telomeric enhances the stability of cancer cells due to the increased expression of the telomere. This enhances the inhibition of cellular senescence and apoptosis. Genetically engineered tumor-specific and oncolytic viruses can be used to target the telomere-telomerase axis (Garg et al.,2015). This leads to the cell death of tumor cells, which increases the production of telomerase. Telomelysin is a genetically induced oncolytic virus that selectively induces cancer cells apoptosis due to the release of neoantigens(Garg et al.,2015). The expression levels of telomerase decrease.

What has changed or added to the original hallmarks and characteristics since the 2011 publication

Enabling characteristics a consequence of favorable conditions of neoplasia whereby the tumor cells can adopt functional traits were added. Also, the tumor microenvironment consists of tumor cells, cancer stromal cells, including stromal fibroblasts, immune cells, and endothelial cells, along with an integral part it plays in tumor survival, pathogenesis, and progression of the malignancy (Hanahan ,2022). In addition, prospective hallmarks understudy added are unlocking phenotypic plasticity where disruptions in cellular differentiation are enhanced and nonmutational epigenetic programming, a process where organisms' genotype interacts with the environment to produce its phenotype (Hanahan ,2022). Others are senescent cells by initiating changes in cell morphology, and cessation of cell division and polymorphic microbiomes that directly and indirectly affect tumor cells and its progression.

Question 2

What physiological differences between S. pombe and S. cerevisiae make them useful yet complementary tools for studying the molecular mechanisms involved in cell cycle regulation and control?

The cell cycle in S. cerevisiae is controlled at the G1/S phase transition through the regulation of the CDC28 protein kinase activity allowing for the study of the G1-S phase. G2/M phase transition is also controlled by CDC28 protein kinase in S. pombe, a fission yeast that can also be studied (Dr. Samanthi, 2020). The encoding genes of S. cerevisiae are approximately 5800 proteins; however, a significant portion is not functional homologs, although they are closely related, serving as a proper model for genome evolution. Introns are non-coding sections of an RNA transcript of the DNA, encoding it separated before the RNA molecule is translated into proteins(Dr. Samanthi, 2020). S. cerevisiae has 5% of the introns, while S. pombe has 40%. Both have genes with signalosome, a protein signaling complex in abundance utilized in diverse pathways. However, RNA interference proteins are only present in S. pombe.

They are both strains of yeast which is a unicellular fungus. They are eukaryotic organisms whose cells contain a membrane-bound nucleus that holds the genetic material. The organisms can be easily manipulated genetically (Dr. Samanthi, 2020). S.cerevisiae is budding yeast that reproduces asexually. At the same time, S.pombe is a fission yeast that reproduces by fission, whereby the parent cell divides into two equal cells(Dr. Samanthi, 2020). They can be both cultured and utilized in the development of mutant strains which contain alterations in single genes. The genotype and phenotype of the organisms vary, enabling individual genes of the system to be studied. Also, S. pombe has telomere, centromeric and associated proteins while S. cerevisiae lacks. 

References

Dr.Samanthi. December 10, 2020. Difference Between Saccharomyces cerevisiae and Schizosaccharomyces pombe. https://www.differencebetween.com/difference-between-saccharomyces-cerevisiae-and-schizosaccharomyces-pombe/

Hanahan, D. (2022). Hallmarks of Cancer: New Dimensions. Cancer Discovery, 12(1), 31-46.

Hanahan, D., & Weinberg, R. A. (2011). Hallmarks of cancer: the next generation. Cell, 144(5), 646-674.

Garg, A. D., Maes, H., van Vliet, A. R., & Agostinis, P. (2015). Targeting the hallmarks of cancer with therapy-induced endoplasmic reticulum (ER) stress. Molecular & Cellular Oncology, 2(1), e975089.