Tumor stem cells, which have the potential for self-renewal, unlimited proliferation, and multidirectional differentiation, are present in very small numbers in tumor tissues, and it is these tumor stem cells that contribute to tumorigenesis and development. It is believed that tumor stem cells may arise in two ways: one is the transformation of normal stem cells into tumor stem cells due to changes in the stem cell niche (microenvironment) or genetic mutations; the other is the genetic mutation of rapidly proliferating precursor cells generated by stem cells, which continue to proliferate rapidly without entering a differentiated and mature state. More frequently, mutations cause these only partially differentiated, rapidly proliferating precursor cells to reverse their differentiation into tumor stem cells. Whichever pathway leads to the generation of tumor stem cells is closely related to the stem cell niche. Various signals in the niche regulate the biological behavior of stem cells, and when abnormal signal generation causes abnormal stem cell behavior, it can lead to the transformation of normal stem cells into tumor stem cells. For example, bone forming protein (BMP) provides growth inhibitory signals to stem cells in the niche. Selective inactivation of BMP receptors in mice leads to increased numbers of hair follicle tumors, intestinal polyps, and hematopoietic stem cells. wnt provides growth-promoting signals to stem cells in the niche, and the wnt signaling pathway is activated when wnt binds to its receptor Frizzled. If Wnt signaling is aberrantly activated, it can lead to hair follicle tumors, intestinal adenomatous polyps, and myeloid leukemia. The growth inhibitory signaling of BMP and the growth promoting signaling of Wnt in the small realm together regulate the proliferation of stem cells. Once the balance is disturbed, it may lead to uncontrolled proliferation of stem cells thus transforming into tumor stem cells and initiating tumorigenesis. In addition to signaling abnormalities in small realms, genetic mutations are also important causes of the transformation of normal stem cells into tumor stem cells. For example, some genetic mutations lead to the impairment of stem cell self-renewal mechanism that depends on the regulation of the niche, so that the self-renewal and expansion of stem cells are not regulated by the niche, resulting in the transformation of stem cells into tumor stem cells. Tumor stem cells, which originate from normal stem cells, can secrete factors that recruit cells from the niche to the tumor, resulting in the expansion of the stem cell niche. Tumor stem cells also expand with the expansion of stem cell niche. Under the influence of tumor stem cells or the microenvironment of the niche, the cells in the niche also expand and undergo some genetic mutations. The tumor stem cells recruit the mutated niche cells around themselves to form a new niche. The new niche provides a signal for the tumor stem cells to renew themselves, and the tumor stem cells quickly adapt to the new niche, renew themselves in the new niche and produce differentiated tumor cells. Some tumor stem cells can also develop into tumor stem cells that self-renew spontaneously without relying on the niche. The above process is likely to be one of the important mechanisms for tumor invasion of surrounding tissues, or distant formation of metastases. 2. Reverse differentiation of partially differentiated progeny cells into tumor stem cells Gene mutations can also occur in transiently proliferating precursor cells (progeny cells of stem cells), which are partially differentiated cells. Mutations cause these partially differentiated transiently proliferating cells to not continue to differentiate into mature cells, but retain the ability to proliferate rapidly. A large number of rapidly proliferating immature cells form a pool of cells in which some molecular or genetic events occur to reverse the differentiation of the rapidly proliferating partially differentiated cells into tumor stem cells. Ma Wang, Department of Oncology, First Affiliated Hospital of Zhengzhou University The partially differentiated daughter cells that have left the stem cell niche may return to the niche and return to the stem cell state under the action of the niche microenvironment, a process called retrodifferentiation. In the process of reverse differentiation of differentiated cells to return to the stem cell state, if the microenvironment of the niche is abnormal or the cell gene is mutated, it will also lead to the generation of tumor stem cells. 3.Relationship between migration and mobilization of stem cells in small realm and tumor invasion and metastasis The molecular mechanisms of migration and mobilization of normal stem cells and tumor invasion and metastasis are somewhat similar. Some factors are necessary in the process of mobilization of normal stem cells as well as in the process of invasion and metastasis of tumor cells. For example, the activation and mobilization of hematopoietic stem cells mentioned earlier requires matrix metalloproteinase-9 (MMP-9) to hydrolyze extracellular matrix components. Matrix metalloproteinase 9 also converts stem cell factors from a membrane-anchored state to a free state, and free state stem cell factors contribute to the activation and mobilization of hematopoietic stem cells in the cellular compartment. The matrix metalloproteinase family is also a key molecule in the invasion and metastasis of malignant tumors. In addition, the migration of hematopoietic stem cells and neural stem cells requires integral proteins, which are also involved in tumor invasion and metastasis. The previously mentioned chemokine CXCL12 and its specific receptor CXCR4 play a crucial role in stem cell mobilization, and CXCL12 was also found to be closely associated with breast cancer cell migration. Thus, there may be a theoretical link between stem cell mobilization and tumor cell invasion and metastasis.