Fibroblasts in the tumor microenvironment secrete molecules like MMPs, cytokines and growth factors that stimulate tumor cell growth and progression. Studies have shown that fibroblast gene expression is altered in the tumor environment, and microRNAs play a key role in regulating these changes. Specifically, fibroblast microRNAs control tumor cell motility and invasiveness. The tumor suppressor p53 acts as both a transcriptional activator and repressor in response to cellular stress. It represses genes involved in cell cycle progression like PLK1 and Cdc25c. Understanding the dynamics between tumor cells and the microenvironment is important for developing strategies to prevent metastasis.

1. FIBROBLAST MICRO RNAs REGULATE TUMOR CELL AND p53 INDUCE TRANSCRIPTIONAL REPRESSION LUISA FERNANDA GUARIN HINCAPIE MEDICINE STUDENT – UPB – 2011

2. FOLDING

3. FOLDING

4. INTRODUCCTION

5. MICRO RNAs ARE INVADING THE TUMOR MICROENVIRONMENT: FIBROBLAST MICRO RNAs REGULATE TUMOR CELL MOTILITY AND INVASIVENESS. Cell Cycle (Dic 7-2010)

6. MICRO RNAs ARE INVADING THE TUMOR MICROENVIRONMENT: FIBROBLAST MICRO RNAs REGULATE TUMOR CELL MOTILITY AND INVASIVENESS. Cell Cycle (Dic 7-2010) Malignant tumor cells interact all the time with stroma elements, they control tumor progression spreading, and response to therapy; cancer associated fibroblasts (CAFs) participate at all stages of tumor growth and progression

7. MICRO RNAs ARE INVADING THE TUMOR MICROENVIRONMENT: FIBROBLAST MICRO RNAs REGULATE TUMOR CELL MOTILITY AND INVASIVENESS. Cell Cycle (Dic 7-2010) But CAFs are not normal fibroblasts; they stimulate tumor cells by secreting MMPs, cytokines and growth factors. Studies suggest that the alteration gene expression is the result of mechanisms pre- existing or induce by tumor cell inflammation or specific tumor tissue conditions.

8. MICRO RNAs ARE INVADING THE TUMOR MICROENVIRONMENT: FIBROBLAST MICRO RNAs REGULATE TUMOR CELL MOTILITY AND INVASIVENESS. Cell Cycle (Dic 7-2010) Micro RNAs is necessary for a normal development even in cancer; miRNAs repress expression of targeting genes by inhibiting them translation or inducing mRNA degradation. Now we know that the unique role of CAFs in humans is tumor cells motility.

9. PERSONAL OPINION

10. P53, TRANSCRIPTIONAL REPRESSION AND DRUG SENSITIVITY: FRESH PERSPECTIVES ON AN OLD ACTIVITY Cell Cycle (Dic 7-2010)

11. P53, TRANSCRIPTIONAL REPRESSION AND DRUG SENSITIVITY: FRESH PERSPECTIVES ON AN OLD ACTIVITY Cell Cycle (Dic 7-2010) P53 tumor suppressor becomes as a transcription factor after suffer cellular stress (DNA damage, hypoxia, etc.); now p53 can be a transcriptional activator or transcriptional repressor of gene expression.

12. P53, TRANSCRIPTIONAL REPRESSION AND DRUG SENSITIVITY: FRESH PERSPECTIVES ON AN OLD ACTIVITY Cell Cycle (Dic 7-2010) p53can induce cell cycle arrest and apoptosis. The transcriptional repression by p53 of the gene encoding Polo like kinases (PLK1) and Cdc25c, both participate in the cycle cell checkpoint and belong to CDE/CHR elements (cell cycle dependent element/cell cycle genes homology region).

13. P53, TRANSCRIPTIONAL REPRESSION AND DRUG SENSITIVITY: FRESH PERSPECTIVES ON AN OLD ACTIVITY Cell Cycle (Dic 7-2010) PLK1 and Cdc25c are typically repressed in non-cycling (normal) cells, and over expressed in tumor cells with mutant p53.

14. PERSONAL OPINION

15. MEDICAL UTILITY

16. MEDICAL UTILITY MICRO RNAs ARE INVADING THE TUMOR MICROENVIRONMENT: FIBROBLAST MICRO RNAs REGULATE TUMOR CELL MOTILITY AND INVASIVENESS. Cell Cycle (Dic 7-2010) When a patient has cancer is important tray to avoid a metastatic cancer and the fact to understand the dynamic is so important, that is why is so important to go deeper with CAFs studies.

17. MEDICAL UTILITY P53, TRANSCRIPTIONAL REPRESSION AND DRUG SENSITIVITY: FRESH PERSPECTIVES ON AN OLD ACTIVITY The tumors can be so aggressive with human body, they should be detected as soon as possible; technology has contributed with many diagnostic methods giving us the possibility to save lives.

18. BIBLIOGRAPHY MARTINEZ S., Lina María. Biología molecular. 5. ed. Medellín : UPB. Fac. de Medicina, 2009. Shurin MR. Micro RNAs are invading the tumor microenvironment: Fibroblast micro RNAs regulate tumor cell motility and invasiveness. Cell Cycle. 2010 Dec7;9(22):4430-1. Pub Med PMID: 21088483. Murphy ME. p53, transcriptional, and drug sensitivity: fresh perspectives onan old activity. Cell Cycle. 2010 Dec 7;9(22):4432. Pub Med PMID: 21188768.

19. LUISA FERNANDA GUARIN HINCAPIE THANKS A LOT