PIN1 is a member of peptidylprolyl isomerases family that binds phosphoproteins and catalyzes the rapid
cis–trans isomerization of proline peptidyl bonds, resulting in an alteration of protein structure, function
and stability. PIN1 was found overexpressed in human cancers and promotes tumorigenesis, althought,
depending on the cellular context, it also acts as a tumor suppressor.
Here, we found that PIN1 is overexpressed in serous ovarian cancer patients and show that PIN1 is a new
oncogene in this type of cancer. PIN1 inhibition in different ovarian cancer cell lines affected cancer cell
viability and promoted cell death via activation of apoptotic program.
Since few therapies are effective against ovarian cancer because almost all patients develop resistance to
conventional treatments, we hypothesized that PIN1 could be a potential therapeutic target. We identified
a small molecule (VS10) that selectively binds and inhibits PIN1 as demonstrated by decreased levels of
the PIN1 downstream targets β-catenin, cyclin D1 and pSer473-Akt in VS10-treated cells. Moreover,
VS10 reduced the viability of four ovarian cancer cell lines. These results suggest that PIN1 might be an
efficient and selective PIN1 inhibitor which could offer a new opportunity for treating PIN1-
overexpressing tumors.
PIN1 is a member of peptidylprolyl isomerases family that binds phosphoproteins and catalyzes the rapid
cis–trans isomerization of proline peptidyl bonds, resulting in an alteration of protein structure, function
and stability. PIN1 was found overexpressed in human cancers and promotes tumorigenesis, althought,
depending on the cellular context, it also acts as a tumor suppressor.
Here, we found that PIN1 is overexpressed in serous ovarian cancer patients and show that PIN1 is a new
oncogene in this type of cancer. PIN1 inhibition in different ovarian cancer cell lines affected cancer cell
viability and promoted cell death via activation of apoptotic program.
Since few therapies are effective against ovarian cancer because almost all patients develop resistance to
conventional treatments, we hypothesized that PIN1 could be a potential therapeutic target. We identified
a small molecule (VS10) that selectively binds and inhibits PIN1 as demonstrated by decreased levels of
the PIN1 downstream targets β-catenin, cyclin D1 and pSer473-Akt in VS10-treated cells. Moreover,
VS10 reduced the viability of four ovarian cancer cell lines. These results suggest that PIN1 might be an
efficient and selective PIN1 inhibitor which could offer a new opportunity for treating PIN1-
overexpressing tumors.
