Rabbit Anti-Human LATS2 (internal) Polyclonal antibody

Chronic lymphocytic leukemia (CLL) is characterized by the accumulation of the malign lymphocytes in the bone marrow and blood. LATS2 (Large Tumor Suppressor Homolog 2) is an important component of the Hippo pathway, which plays a crucial role in regulation of apoptosis, proliferation and cell growth. The present study was designed to determine the interactions between LATS2 (Large Tumor Suppressor Homolog-2) expression on risk of Chronic lymphocytic leukemia (CLL). In 28 patients with CLL and 20 controls, LATS2-mRNA and LATS2-protein expressions were measured by quantitative reverse-transcription-PCR and Western blotting techniques, respectively. The LATS2 expressions were down-regulated in the CLL group compared to the controls. We observed that the percentage of CD20 was higher in CLL subjects with the LATS2-mRNA Fold change (FC) of <= 0.1 than those with the LATS-mRNA FC of > 0.1 (p= 0.057), while interestingly, the percentage of CD3, CD8, and CD56 T-cell markers was lower in CLL subjects with the FC of <= 0.1 than those with the LATS2-mRNA FC of > 0.1 (p= 0.004, p= 0.008 and p= 0.058, respectively). The relationships among between the immunophenotypically determined B-cell marker-CD20, T cell markers-CD3, CD8 and CD56 and LATS2-mRNA levels may suggest possible diagnostic/prognostic value of LATS2 in CLL. We suppose that these markers may be significant indicators of the severity or advanced stages of the CLL.

Sphingosylphosphorylcholine (SPC) is a bioactive sphingolipid which regulates many cancer-related processes, including cellular proliferation. The Hippo signaling pathway consists of a cascade of tumor suppressive kinases Mst1/2 and Lats1/2 and their downstream targets YAP and TAZ which are generally pro-proliferative transcriptional regulators. Direct phosphorylation by Lats1/2 causes inhibition or degradation of YAP/TAZ and down-regulation of their target genes. We found SPC treatment of MDA-MB-435S breast cancer cells to strongly inhibit their proliferation and to induce a sustained Lats2 protein expression (6-24 h). Therefore, we hypothesized that Hippo signaling might mediate the anti-proliferative SPC response. We also saw a cell density-dependent increase in S127-phosphorylated YAP (pS127-YAP) and a decrease in mRNA levels of YAP target genes (CTGF, Cyr61) in response to long (9 h) SPC treatment. Knockdown of SIP receptor 2 (S1P(2)) prevented the SPC-induced up-regulation of Lats2 and attenuated the anti-proliferative effect of SPC. However, while knockdown of Lats2 alone or in combination with Lats1 expectedly increased basal proliferation it did not attenuate the SPC-induced inhibition of proliferation. Exogenous expression of wild-type or kinase-dead Lats2 and knockdown of YAP/TAZ also had no effect on the anti-proliferative SPC response. It has been previously shown that activation of S1P(2)-G(12/13) by sphingosine-1-phosphate (SIP) leads to rapid de-phosphorylation and up-regulation of YAP. Similarly, we saw a decrease in pS127-YAP and an increase in total YAP levels with short (1 h) SPC treatment as well as a subsequent transient increase in YAP target gene expression. Inhibition of S1P2 prevented the SPC-induced YAP dephosphorylation. The rapid YAP activation and subsequent up-regulation of Lats2 mRNA does not constitute a negative feedback loop as knockdown of YAP/TAZ did not inhibit SPC-induced Lats2 expression. In conclusion, in this study we show that SPC is able to regulate Hippo signaling in a dual and opposite manner, causing an initial activation of YAP followed by an inhibition. However, even the strong SPC-induced effects seen in Lats2 and YAP did not mediate the anti-proliferative SPC response. (C) 2016 Elsevier Inc. All rights reserved.