In pluripotent stem cells and cancer, suppression of lysosomal and autophagic function is directly downstream of c-MYC overexpression and may represent a hallmark of malignant transformation.
Two recent studies of lymphoma and breast cancer have identified components of the spliceosome - the core splicing machinery - that are essential for malignant transformation driven by the transcription factor MYC.
Deconstructing the epidemiological association between GBC and Salmonella Typhi infection, we show that Salmonella enterica induces malignant transformation in predisposed mice, murine gallbladder organoids, and fibroblasts, with TP53 mutations and c-MYC amplification.
In addition, we observed an over-expression of another MYC family gene member, MYCN that may therefore represent a cooperating mechanism of MYC in driving the malignant transformation in those cases lacking an identifiable MYC translocation but expressing the gene at the mRNA and protein levels.
MYC contributes to malignant transformation by promoting multiple processes including uncontrolled cell proliferation, cell growth and genomic instability.
Accordingly, MYC is recognized as a major driver of T-cell acute lymphoblastic leukemia (T-ALL) in human and zebrafish/mouse models, and uncovering the context by which MYC-mediated malignant transformation initiates and develops remains a considerable challenge.
These subclonal cell lines showed changes in growth pattern and morphology, as well as a karyotype drift concomitant with the overexpression of genes commonly involved in malignant transformation (c-MYC, EGFR, HIF-1alpha and LDH-A).
MYC is an important oncogene in hematopoietic neoplasms in humans, yet the mechanism by which MYC induces the malignant transformation of blood cells has remained elusive.
Uteroglobin promoter-targeted c-MYC expression in transgenic mice cause hyperplasia of Clara cells and malignant transformation of T-lymphoblasts and tubular epithelial cells.
Ever since Bishop and his co-workers discovered the c-myc gene in the late 1970s (Bishop 1982), voluminous literature has documented its central role in proliferation and malignant transformation of human and animal cells (Amati et al.1998, Bouchard et al.1998, Dang et al.1999).
C-myc gene activation is a common event in multiple types of neoplasia and has been associated with different cellular processes relevant to the malignant transformation of cancer cells.
One possible reason is that the increased expression of the c-myc protein is not sufficient alone to promote proliferation and malignant transformation in these types of tumors.
Finally, we demonstrate that, like the N- and c-myc genes, the L-myc gene can cooperate with a mutant Ha-ras gene to cause malignant transformation of rat embryo fibroblasts in culture.