Two stages involved in cancer stem cell activation. Cancer requires the generation of an actively dividing or “activated” stem cell. This cell may be an actively dividing stem cell, a stem cell stimulated to divide by tissue damage or inflammation, or from an a differentiated (mature) cell acquiring the property of self-renewal. Mutations inactivating tumor suppressor genes (negative regulators of growth) or activating oncogenes (positive regulators) convert the activated stem cell into a cancer stem cell. Further mutations are required for tumor progression and metastasis.