Securin is Required for Chromosomal Stability in Human Cells

C03816: Securin is Required for Chromosomal Stability in Human Cells

Value Proposition:

ADVANTAGES

Technical Details:

BACKGROUND

Genetic instability is now widely recognized as an essential factor in the evolution of cancer. In a majority of solid tumors, genetic instability tends to be involved in the gains and losses of whole or partial chromosomes leading to aneuploidy. This aneuploidy has recently been explained by chromosomal instability (CIN), an accelerated rate of gain or loss of whole or large portions of chromosomes. Securin, which is involved in chromatid separation, has transforming activity in vitro, is over-expressed in many tumours, and causes aneuploidy directly associated with CIN and subsequently cancer. There is a current need for therapeutic agents which are selectively toxic to aneuploid cells relative to euploid cells. TECHNOLOGY JHU scientists have developed materials and methods which are useful for screening potential anti-tumor agents. Human securing was deleted by homologous recombination in HCT116 cells. In culture the hSecurin-/- cells grow a bit slower than wildtype cells but the homozygous loss of securin is not lethal to human cells. These homozygous securin-defective cells fail to separate their metaphase chromosomes appropriately and as a result have budded nuclei, chromosome instability, and gross aneuploidy. The hSecurin-/- cells are able to enter mitosis normally, but then exhibit a major defect in the execution of anaphase. hSecurin-/- cells contained many chromosome losses, with 80% of metaphases exhibiting at least one chromosome loss with individual metaphases missing as many as 21 chromosomes.

Looking for Partners:

Commercial application includes Cells lines that can screen potential therapeutic agents for their ability to preferentially inhibit or kill homozygous securing-defective cells relative to securing-proficient cells.

Publications/Associated Cases:

Jallepalli, P. V., Waizenegger, I. C., Bunz, F., Langer, S., Speicher, M. R., Peters, J. -., et al. (2001). Securin is required for chromosomal stability in human cells. Cell, 105(4), 445-457. Issued US Patent: US 7354703 entitled “Securin is required for chromosomal stability in human cells”.

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