Figure 1

Schematic definition of the process of oncoprotein metastasis (OPM) accompanied by physical interactions between oncoproteins (OPs) and tumor suppressor proteins (TSPs): a) spatially, consisting in the local, tissular penetration of OPs into cells adjacent to the cells from which the OPs originate (thereby extending the paracrine principle) and/or their systemic spread via blood and lymphatic vessels to distant tissues/organs (thereby extending the endocrine principle), each of which would be ensued by (e.g. nucleocrine [28, 31]) OP-TSP complex formations (OP × TSP); it should be also stated here that the OP-secreting cells are not necessarily tumor cells, but could be normal cells, e.g. pancreatic β-cells that secrete (excessive amounts of) insulin in response to (blood-borne) tumoral stimuli and thus cause a well-known (cancer-associated) state of hyperinsulinemia; b) temporally, consisting in the OPM-associated and carcinogenesis-initiating event of OP-TSP complex formations (OP × TSP) that precede the epigenetic silencing of the corresponding tumor suppressor gene-caused by the hypermethylation of its promoter-which in turn is subsequently functionally mimicked by a loss of heterozygosity (LOH) of the same gene, all of which changes would occur in (morphologically) normal, yet likely premalignant cells.