• Investigating of impotence of RAS Signaling in Cancer Metastasis
  • Yasaman Peirovy,1,*
    1. Msc of Molecular Genetic Department of Genetics, Zanjan Branch, Islamic Azad University, Zanjan, Iran.


  • Introduction: When cancerous cells separate from the primary tumor, they can travel to other parts of the body through the circulation or lymphatic system. The majority of metastatic malignancies can be controlled but not cured. Treatment can reduce your symptom burden, halt the spread of the cancer, and enhance your quality of life. The RAS family includes some of the earliest oncogenes to be identified, and its identification completely changed how we think about the biology of cancer. The RAS oncogenes, which were first discovered in the 1960s as a viral component that caused the development of sarcomas in rats, were later discovered to be typical elements of the human genome that were capable of converting healthy human cells. This study looked into the ineffectiveness of RAS signaling non-cancer metastasis.
  • Methods: this review investigating of impotence of ras signaling in cancer metastasis has been written from scientific databases such as Science Direct, Springer, Google Scholar, and PubMed.
  • Results: In addition to driving processes essential for the early phases of tumorigenesis, RAS activity is important for the acquisition of more malignant features, including supporting metastasis. In mouse models of colorectal cancer, while primary tumors were characterized by a heterogeneous population of cells bearing both oncogenic KRAS mutations and wild-type KRAS, metastatic sites were largely comprised of more uniform cell populations harbouring oncogenic KRAS. This metastatic phenotype was promoted by transforming growth factor beta (TGF-β) signaling. Distinct from heterogeneity in cellular populations with respect to KRAS mutation status, the acquisition of multiple oncogenic KRAS mutations within single cells through focal amplifications and loss of the wild-type allele (loss of heterozygosity) can promote tumor metastasis and aggressive properties KRAS also supports metastatic dissemination through repression of Raf Kinase Inhibitory Protein (RKIP), a putative tumor suppressor with roles in cell migration, motility, and epithelial-to-mesenchymal transition. Activation of KRAS signaling along with homozygous deletion of LKB1 also known as STK11 or serine/threonine kinase promoted cancer progression and metastasis in non-small cell lung cancer models. In KRAS-driven pancreatic cancer models, deletion of LKB1 enhanced the tumorigenicity and proliferation rate of cancer cells through enhanced serine biosynthesis and S-adenosyl-methionine (SAM), which supports DNA methylation.
  • Conclusion: RAS family members are some of the most commonly altered genes in cancer. Perturbations of RAS signaling establish robust oncogenic circuits that drive tumor initiation, progression, growth, and survival. Despite our deep knowledge of the direct downstream signaling effectors of the RAS pathway, continued exploration has revealed new insights into the similarities and differences between RAS family members and their preference for particular cancer types. These efforts have also uncovered the more distal downstream consequences of RAS signaling across cancers, including its rewiring of cellular metabolism and capacity to unlock nutrient scavenging pathways, its role in metastasis, and its dual role in regulating the immune microenvironment. These processes endow cancer cells with the plasticity required for survival in dynamic conditions but also create key vulnerabilities, which can be therapeutically targeted through a number of avenues. Taken together, a deeper understanding of RAS biology will critically inform clinical care and serve as a model for interrogation of other driver alterations in cancer.
  • Keywords: RAS signalling, Cancer, Metastasis