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Based on this article http://biotech.bio5.org/sites/default/files/pdf/hallmarks_

ID: 86488 • Letter: B

Question

Based on this article http://biotech.bio5.org/sites/default/files/pdf/hallmarks_of_cancer.pdf if it doesn't work just google "The hallmarks of cancer pdf" It should be the first one on the list.

Only read the Tissue Invasion and Metastasis portion to answer the question

How might cells acquiring this capability as they are discussed in “hallmarks” What are some of the mutations that cancers have that allow them to acquire this hallmark. Why is this important: What are some therapeutics or other interesting stuff that might result if we understood this better?

Please respond in great detail and using own words. Thank you

Explanation / Answer

Cells might be acquiring six hallmark capabilities as follows:

1.Self Sufficiency in Growth signals acquired by activating H-Ras oncogenes.

2. Insensitivity to anti growth signals acquired by losing Retinoblastoma suppressor.

3. Evading Apoptosis by producing IGF survival factor.

4. Limitless potential of replication by turning on Telomerase.

5. Sustained Angiogenesis by producing VEGF inducers.

6.Tissue invasion and Metastasis by inactivating E-cadherin.

Mutations that cancers have that allow them to acquire this hallmark are as follws:

1. In most of the cancers, the function of E-cadherin is lost due to mutation that inactivatesE cadherin, represses transcription, and performs proteolysis of extracellular cadherin domain.

2. N-CAM in immunoglobulins changes into poorly adhesive isoform from a highly adhesive one and develops reduced level of expression.

3. Cancer cells invade by shifting their spectrum of Integrins to alpha and beta subunits displayed by migrating cells.

4. In many cancer cells, matrix degrading proteases are produced by stromal and inflammatory cells rather than epithelial cancer cells.

Understanding the causes and mechanism of cancer is important because at molecular level the regulatory circuits of cancer differ from one tissue environment to another.

The acquired capability for invasion and metastasis is the only source for further exploratory research on cancer. Continuosly evolving analytical techniques will soon construct detailed profiles of expression and functional activities of Proteases, Integrins, and CAMs in many types of cancers, both before and after they acquire invasive and metastatic activities.

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