Cancer Biology Jasmina Makarevic ATTA-UR-RAHMAN SCHOOL OF APPLIED BIOSCIENCES (ASAB) Cancer Biology Jasmina Makarevic Fall Semester 2016

Stem cells Def: Cell type within a tissue that is capable of selfrenewal and is also capable of generating daughter cells that develope new phenotypes, including those that are more differentiated than the phanotype of stem cell. Jasmina Makarevic

Cancer cells and stem cells ES cells and cancer cells can form teratomas (benigne tumors formed by embryonic stem cells in which a wide variety of differentiated cell types are found). They are difusse mess of cells. Many of the stem cell surface receptors are also expressed on cancer cells. Similar genes are expressed in both cell types. Also a ras-like gene Eras is expressed in mouse ES cells, which may give these cells tumor-like properties. Cancer Cells acquire the machanery for cell proliferation that is expressed in tissue stem cells. But what they lose: Feedback systems to know when to stop proliferation and to start differentiating! Jasmina Makarevic

Transformation of stem cells? Are stem cells the targets for carcinogenic transformation? Reya et al.: Stem cells already have the machinery for self-renewal turned on and it would require fewer genetic or epigenetic manipulations for a cell to be- come a cancer cell than if they had to turn all these genes in the novo. Stem cells by their vary of nature are set up to proliferation for several population doublings and thus have a greater oppurtunity for carcino- genic mutations to accumlate than in most mature cell types. Cancer cells lose the ability of differantiation after progression! Jasmina Makarevic

Growth Factors Jasmina Makarevic

How does GF work? As protein kinasen- an enzyme that removes a high-energy phosphat group from ATP and transfer s it to a suitable protein substrat. Jasmina Makarevic

Actions of protein kinases One protein kinase can phosphorylate multiple distinct substrat proteins within a cell. Jasmina Makarevic

Structure of the EGF receptors Cytoplasmic domain once activated emits signals that induce a cell to grow or divide: Cytoplasmic domain activated proceeds to phosphorylate tyrosines on certain Cytoplasmic proteins and causes proliferation. Jasmina Makarevic

Structure of tyrosine kinase receptors Jasmina Makarevic

Different Growth Factors Jasmina Makarevic

The EGF receptor and v-ErbB An altered growth factor receptor can function as an oncoprotein! Oncoproteins like ErbB2, HER2 or Neu are a kind of truncated EGF receptors which don not need ligands to be activated! Jasmina Makarevic

Deregulation of receptor firing Jasmina Makarevic

Tyrosin kinase GF receptors Summary statistics (2012) Tyrosin kinase GF receptors Jasmina Makarevic

Autocrine growth factors in human tumors Jasmina Makarevic

Notch-Receptor Active form of Notch function as an Transcription Factor! Jasmina Makarevic

The Patched- Smoothened Signaling System Jasmina Makarevic

The ras signaling cycle GEF: Guanin nucleotid factor GAP: GTP-ase activating proteins Jasmina Makarevic

Alternative mechanisms of transformation by Ras Ras also can also aktivate EGF receptora upstream!!! Jasmina Makarevic

Summary statistics (2012) Conclusion Without Growth factors, they would not be an activation of the cell signaling pathways and no proliferation! In the next lecture we will have a closer look: Important cell signaling pathways Cell Cycle check points/Tumor supressor genes Jasmina Makarevic

Thank You for Your Attention! Jasmina Makarevic