KAI1 is capable of inhibiting the metastatic process in experimental animals. The expression of the KAI1
gene is also downregulated during tumor progression of prostate, breast, lung, bladder, and pancreatic cancers in
humans, and this downregulation appears to be at the level of transcription or posttranscription. Dong et al. (1995) isolated the metastasis suppressor gene on 11p11.2 by PCR methods and designated it KAI1 for
'kang ai' (Chinese for anticancer). Expression of this gene was reduced in human cell lines derived from metastatic
prostate tumors. KAI1 specifies a protein of 267 amino acids, with 4 hydrophobic and presumably transmembrane
domains and 1 large extracellular hydrophilic domain with 3 potential N-glycosylation sites. KAI1 is evolutionarily
conserved, is expressed in many human tissues, and encodes a member of a structurally distinct family of leukocyte
surface glycoproteins. Decreased expression of this gene may be involved in the malignant progression of prostate and
other cancers. The gene has also been referred to as ST6.
This metastasis suppressor gene product is a membrane glycoprotein that is a member of the transmembrane 4 superfamily. Expression of this gene has been shown to be downregulated in tumor progression of human cancers and can be activated by p53 through a consensus binding sequence in the promoter. Its expression and that of p53 are strongly correlated, and the loss of expression of these two proteins is associated with poor survival for prostate cancer patients.
Cell adhesion molecule
Expression regulated by
Houle CD,et al 2002 reported that loss of expression and altered localization of KAI1 and CD9
protein are associated with epithelial ovarian cancer
Impairment of cell adhesion plays a vital role in tumor
progression. E- and N-cadherin, CD9, and KAI1 are all adhesion molecules that
have been implicated in the progression of several different tumor types. To
help explain the potential role these adhesion molecules have in ovarian
cancer, comparisons were made between expression patterns in normal ovary and
various grades of primary and metastatic epithelial ovarian cancers.
Thirty-two primary and 8 metastatic human ovarian epithelial
carcinomas and 18 samples of normal ovarian tissue were examined for adhesion
molecule expression using immunohistochemistry.
KAI1 and CD9 revealed an inverse relationship between tumor grade and
expression levels, characterized by high expression in low-grade tumors and
low expression in high-grade tumors and metastases. KAI1 and CD9 also
demonstrated a shift in cellular localization from the membrane in grade 1
tumors to the cytoplasm in grade 3 tumors. N-cadherin expression showed a
positive trend between expression levels and tumor grade. E-cadherin
expression varied little between different tumor grades and metastases.
Inclusion cysts (n = 6) and surface invaginations often strongly expressed
KAI1, CD9, and E-cadherin. KAI1 expression was variable in ovarian follicles
and corpora lutea depending on their stage of development.
Although sample size is limited, these findings suggest that
progression of ovarian epithelial carcinomas is associated with
down-regulation and altered cellular localization of KAI1 and CD9. In
addition, variable KAI1 expression during follicular and luteal development
suggests that it has a physiological function in the ovary. Further
investigation will be needed to see if it is also regulated this way during
progression of ovarian cancers.