focal adhesion, cell motility is increased. P27 can also be exported to the cytoplasm by oncogenic activation of the P13K pathway. Thus, mislocalization of p27 to the cytoplasm in cancer cells allows them to proliferate unchecked and provides for increased motility. In contrast to these results, p27 has also been shown to be an inhibitor of migration in sarcoma cells. In these cells, p27 bound to stathmin which prevents stathmin from binding to tubulin and thus polymerization of microtubules increased and cell motility decreased. MicroRNA regulation Studies of various cell lines including glioblastoma cell lines, three prostate cancer cell lines, and a breast tumor cell line showed that suppressing miR-221 and miR-22 expression resulted in p27-dependent G1 growth arrest Then when p27 was knocked down, cell growth resumed indicating a strong role for miRNA regulated p27. Studies in patients have demonstrated an inverse correlation between miR-221&22 and p27 protein levels. Additionally nearby healthy tissue showed high expression of the p27 protein while miR-221&22 concentrations were low. Regulation in specific cancers In most cancers reduced levels of nuclear p27 are correlated with increased tumor size, increased tumor grade, and a higher propensity for metastasis. However the mechanisms by which levels of p27 are regulated vary between cancers. Breast In breast cancer, Src activation has been shown to correlate with low levels of p27 Breast cancers that were Estrogen receptor negative and progesterone receptor negative were more likely to display low levels of p27 and more likely to have a high tumor grade. Similarly, breast cancer patients with BRCA1/2 mutations were more likely to have low levels of p27. Prostate A mutation in the CDKN1B gene has been linked to an increased risk for hereditary prostate cancer in humans. Multiple Endocrine Neoplasia Mutations in the CDKN1B gene has been reported in families affected by the development of primary hyperparathyroidism and pituitary adenomas, and has been classified MEN4 (multiple endocrine neoplasia, type 4). Testing for CDKN1B mutations has been recommended in patients with suspected MEN, in whom previous testing for, the more common MEN1/RET mutation, is negative. Clinical significance Prognostic value Several studies have demonstrated that reduced p27 levels indicate a poorer patient prognosis. However, because of the dual, contrasting roles p27 plays in cancer (as an inhibitor of growth and as a mechanism for metastasis) low levels of p27 may demonstrate that a cancer is not aggressive and will remain benign. In