Cancer Cell Biology PDF BS31004

Cancer Cell Biology BS31004 Biochemistry and Cell Biology Ying Liu ([email protected])  Explain the Molecular Basis of Tumorigenesis Intended Distinguish Between Oncogenes and Tumor Suppressor Genes Learning Outline the Mechanisms of Epithelial- Outcomes Mesen...

Cancer Cell Biology BS31004 Biochemistry and Cell Biology Ying Liu ([email protected])  Explain the Molecular Basis of Tumorigenesis Intended Distinguish Between Oncogenes and Tumor Suppressor Genes Learning Outline the Mechanisms of Epithelial- Outcomes Mesenchymal Transition and metastasis Describe Methods for Cancer Diagnosis and Treatment  Cancer Overview Oncogenes and Tumor Overview Suppressor Genes Primary Tumor Formation EMT and Metastasis  Cancer Overview Two properties of cancer cells: proliferation in defiance of the normal constraints; metastasis, invade and colonize territories normally reserved for other cells Cells that only have proliferation produce primary (benign) tumors, which can be surgically removed Secondary Cancer Secondary (malignant) They then have to exit tumor cells must cross from the bloodstream or the basal lamina, migrate lymph and settle, survive through connective and proliferate in a new tissue, and get into blood location or lymphatic vessels  Cancer Cells Accumulate Mutations Cancers develop by an Green: mutation for Green to purple: mutation accumulation of mutations, avoiding cell death to be independent from mostly somatic mutations (apoptosis) growth factor regulation  Cancer Cells Accumulate Mutations This breast cancer cell has Multiple translocations can Mutations in cell adhesion highly abnormal be seen, and the cell molecules are important chromosomes, reflecting contains 48 chromosomes for metastasis genetic instability instead of the normal 46 Characteristics of Cancer Cells Lack of differentiation Do not contribute to body function Have abnormal nuclei that are enlarged and may have abnormal # of chromosomes Unlimited ability to divide: turn on telomerase gene that allows cells to divide over and over again Cancer Cells Evolve Cancer cells Some cancers evolve by contain multiple repeated rounds malignant clones, of mutation, each with its own proliferation and collection of natural selection mutations At each step, a single cell undergoes a mutation that enhances its ability to proliferate or survive, so that its progeny become a dominant clone in the tumor  Oncogenes Oncogenes act in a dominant manner: a gain-of-function mutations in a single copy of the proto-oncogene can drive a cell toward cancer Examples of proto-oncogenes include: Ras, ERK (MAP Kinase), EGF receptor, and transcription factor myc  Tumor Suppressor Genes Tumor suppressor genes act in a recessive manner: a loss-of-function mutations in both copies of the TS gene can drive a cell toward cancer Examples of tumor suppresser genes include: Rb, p53 and p27  Primary Tumor Formation Primary tumor formation: uncontrolled cell division In normal cells, DNA damage can trigger: ○ DNA repair mechanism ○ Cell cycle arrest ○ Apoptosis (programmed cell death) Primary Tumor Formation In cancer cells with DNA damage, the damage is not repaired The damaged cell does not die as it should Proliferation: all the progeny cells carry the same DNA damage For example, half of human tumors contain a mutation in p53 tumor suppressor gene Tumor Suppressors  Tumor Suppressors BRCA 1 and 2: involved in DNA repair Mutations in either gene increased risk of breast cancer and ovarian cancer  Contact Inhibition Normal cells adhere to their neighbors and exhibit contact inhibition When they come in contact with a neighbor, they stop dividing Cancer cells have lost all restraint and grow on top of each other forming tumor (anti-social) E-Cadherin and Contact Inhibition E-Cadherin: transmembrane glycoprotein that forms part of adherens junctions Essential for maintaining tissue architecture, integrity and polarity Triggers cell cycle arrest when cells are crowded E-Cadherin  EMT Epithelial-Mesenchymal Trasition: Epithelial cells lose their characteristics and gain motility (mesenchymal trait) N-Cadherin: found in mesenchymal cells such as fibroblasts, endothelial cells and neural tissues EMT Claudins and Occludins Claudins and Occludins Metastasis Melanoma  Cancer Diagnosis Early diagnosis: ○ Imaging: X-ray, CT, MRI, ultrasound ○ Blood test for tumor biomarkers ○ Genetic tests for mutations in proto- oncogenes and tumor suppressor genes Cancer Treatment Local (benign) tumor: ○ Surgery ○ Radiation Metastatic cancer: ○ Chemotherapy Immunotherapy ○ Boost body’s immune defenses to fight cancer ○ Vaccines, antibodies, CAR-T cell therapy