The extent to which heterogeneity within mesenchymal stem cell (MSC) populations is related to function is not understood. Using the archetypal MSC in vitro surface marker, CD90/Thy1, here we show that 30% of the MSCs in the continuously growing mouse incisor express CD90/Thy1 and these cells give rise to 30% of the differentiated cell progeny during postnatal development. In adulthood, when growth rate homeostasis is established, the CD90/Thy1⁺ MSCs decrease dramatically in number. When adult incisors are cut, the growth rate increases to rapidly re-establish tooth length and homeostasis. This accelerated growth rate correlates with the re-appearance of CD90/Thy⁺ MSCs and re-establishment of their contribution to cell differentiation. A population of Celsr1⁺ quiescent cells becomes mitotic following clipping and replenishes the CD90/Thy1 population. A sub-population of MSCs thus exists in the mouse incisor, distinguished by expression of CD90/Thy1 that plays a specific role only during periods of increased growth rate.

P21‐activated kinase 5 (PAK5) is the recently identified member of the group B p21‐activated kinase (PAK) family which are effectors of the small GTPase Cdc42 and Rac1, known to regulate cell motility and activate cell‐survival signaling pathways. However, overexpression of PAK5 has not been associated with any cancers so far. Interestingly, we found that PAK5 was overexpressed in a variety of colorectal carcinoma (CRC) cell lines in a Western‐blotting examination. Therefore, in this study, we aim to examine the PAK5 expression during CRC progression and to answer if PAK5 is involved in malignant progression of CRC. By immunohistochemistry, our results showed that PAK5 expression was increased with CRC progression through the adenoma to carcinoma sequence, with the most significant increases in invasive and metastatic CRCs (p < 0.0001). Furthermore, increased PAK5 expression was also found with the development of CRC from lower Duke's grades to higher ones (p < 0.01). Moreover, PAK5 was also increased from well to poorly differentiated CRCs (p < 0.01). Using gain and loss of function experiments, we found that PAK5 reduced CRC cell adhesion but promoted their migration on collagen type I. Taken together, our study demonstrated that PAK5 expression increased significantly with malignant progression of CRC and that PAK5 might promote CRC metastasis by regulating CRC cell adhesion and migration. © 2009 UICC

Kindlin-2 is a novel integrin-interacting focal adhesion protein that belongs to the Kindlin family. Focal adhesion proteins control cytoskeleton dynamics and promote cancer cell growth, survival, migration and metastasis. Little is known, however, about expression of Kindlin-2 in association with human cancer. We now reveal high Kindlin-2 expression in malignant mesothelioma (MM) cell lines using an affinity-purified anti-Kindlin-2 antibody. Furthermore, we show by immunohistochemistry that Kindlin-2 is highly expressed in 92 of 102 (90%) MMs with epitheliod; sarcomatoid, biphasic and poorly differentiated morphologies. In addition, Kindlin-2 expression correlates to cell proliferation, suggesting a role for Kindlin-2 in tumor growth. We also detect increased expression of Kindlin-2 at the invasion front of tumors concurrent with increased expression of integrin-linked kinase, a Kindlin-binding protein. Besides the high expression of Kindlin-2 in pleural MMs, pleural metastases of lung adenocarcinoma also express large amounts of Kindlin-2, but not Kindlin-1. Notably, in vitro, when endogenous Kindlin-2 was knocked down with RNAi in MM cells, this impaired cell spreading, adhesion and migration. Overall, our study suggests that heightened expression of Kindlin-2 might contribute to tumor progression in MM.