Class II Tumor Suppressor Genes (C2TSGs)
The term "Class II tumor suppressor gene" was already proposed in 1997 by Ruth Sager* (here is a tribute to her scientific life) after finding that many genes in a variety of human cancers rather showed strong down regulation (compared to healthy tissue) than being altered by mutation or deletion.
Class II Tumor Suppressor Genes (C2TSGs) usually have a role in negatively regulating different „Hallmarks of Cancer“, e.g. by reducing cell proliferation, reducing cell migration capacity, supporting apoptosis or differentiation or inhibiting tumor invasion and metastasis. Thus tumor cells seek to regulate down these important genes. Already more than 20 years ago, we have started to discover and further characterize a larger number of new putative C2TSGs by a screening procedure involving EST cDNA libraries. A description of the procedure can be found here*. Starting from 600 genes which were found to be differentially expressed in gynecological tumors 40 particularly interesting C2TSGs were selected, which were characterized in greater detail by the German Human Genome Project (DHGP) consortium "Genetic Basis of Gynaecological Carcinomas" (Dahl et al. Abstract*). Later on our research group characterized further putative C2TSGs (and novel putative oncogenes) by molecular profiling of laser-microdissected matched tumor and normal tissues. (Abstract*) and by in silico analysis of databases like TCGA. (Abstract*)
We characterize novel C2TSG candidates by their effect on tumor cell behavior after forced re-expression in different models of human cancer. An example of the strong inhibitory effect of the tumor suppressor gene ITIH5 on the migratory ability of pancreatic cancer cells can be seen here. The video shows the comparison of the migration speed of PSN1 pancreatic cancer cells expressing ITIH5 (ITIH5 clone 11 and 12, lower row) compared to mock transfected cells that do not (mock clone 1 and 3, upper row). The complete publication on the importance of ITIH5 as a tumor suppressor in human pancreatic cancer can be found here. https://pubmed.ncbi.nlm.nih.gov/38375974/
We are convinced that C2TSGs themselves and the pathways regulated by them may offer novel therapeutic approaches to combat cancer, as we have recently published in a white paper on this topic (https://www.mdpi.com/2072-6694/14/18/4386).
