<p>GAS2 Promotes Cell Proliferation and Invasion and Suppresses Apoptosis in Pediatric T-Cell Acute Lymphoblastic Leukemia and Activates Wnt/β-Catenin Pathway</p>

Abstract

Purpose: This study aimed to investigate the effect of growth arrest specific 2 (GAS2) on T-cell acute lymphoblastic leukemia (T-ALL) and its potential molecular mechanism. Methods: The GAS2 expression level was detected by qRT-RCR and Western blot in normal T lymphocytes and TALL cells Jurkat and CCRF-CEM. The proliferation and invasion of Jurkat and CCRF-CEM cells were detected by MTT and Transwell assay, respectively. Apoptosis and cell cycle were measured by flow cytometry. In addition, the chemotherapeutic sensitivity of Jurkat and CCRF-CEM cells was measured MTT assay and flow cytometry. Results: GAS2 was highly expressed in Jurkat and CCRF-CEM cells. GAS2 could promote cell proliferation and invasion, and inhibit apoptosis of Jurkat and CCRF-CEM cells. GAS2 also promoted cell cycle changes from G0/G1 phase to S phase in Jurkat and CCRF-CEM cells. In addition, GAS2 could reduce the chemotherapeutic sensitivity of Jurkat and CCRF-CEM cells. GAS2 overexpression could promote the expression levels of ki67, proliferating cell nuclear antigen (PCNA), Bcl-2, c-myc, cyclin D1 and β-catenin, while GAS2 knockdown could inhibit their expression levels. Meanwhile, GAS2 overexpression could inhibit Bax expression. Moreover, Wnt/β-catenin pathway inhibitor XAV939 could inhibit the expressions of c-myc, cyclin D1 and β-catenin, but activator LiCl could promote their expression. Conclusion: Our study demonstrated that GAS2 could promote cell proliferation and invasion, and induce cell cycle, as well as inhibit apoptosis and could activate the Wnt/βcatenin pathway in TALL cells.

Linalool inhibits the growth of human T cell acute lymphoblastic leukemia cells with involvement of the MAPK signaling pathway

“…A large number of antitumor natural compounds, such as baicalin and homoharringtonine, have demonstrated to induce cell death and apoptosis in close association with cell cycle arrest at the G 1 phase (31,32). Notably, the present study demonstrated that Jurkat cells treated with linalool had reduced cell accumulation at the G 0 /G 1 phase, which contains numerous non-proliferating leukaemia cells (33). The findings of the present study indicate that linalool may affect proliferating and non-proliferating T-ALL cells.…”

Growth arrest–specific 2 protein family: Structure and function

“…GAS2 protein has been reported to promote the growth of several leukaemic cells, such as K562, MEG-01, Jurkat or THP-1 cells. 36,48,51 Further, GAS2 can facilitate the tumour formation of THP-1 cells in nude mice. 51 GAS2 is reportedly involved in the disease transformation of CML 52 and exhibits an opposite effect on the inhibition or emergency granulopoiesis termination roles of ICSBP for leukaemia.…”

“…13,35 In contrast, GAS2 in two T-cell acute lymphoblastic leukaemia cell lines (Jurkat and CCRF-CEM) facilitates the G1-to-S transition of the cell cycle. 36 To date, limited experimental evidence has been found linking the GAS2 family members with the cell cycle. For example, overexpression of GAS2L1 was reported to lengthen the cell cycle and inhibit the growth of stem cell factor/erythropoietin (SCF/EPO)-dependent red cell progenitors.…”

“…Similarly, upregulated GAS2 in a hepatocellular carcinoma (HCC) cell line (SK‐Hep1) suppresses the G1‐to‐S transition of the cell cycle 13,35 . In contrast, GAS2 in two T‐cell acute lymphoblastic leukaemia cell lines (Jurkat and CCRF‐CEM) facilitates the G1‐to‐S transition of the cell cycle 36 …”

“…For chronic myeloid leukaemia (CML), Huang et al provided evidence that the high expression level of GAS2 is associated with increased β‐catenin‐dependent survivin expression, resulting in a Fas‐induced apoptosis resistance status in Bcr‐Abl‐positive or ICSBP‐knockout myeloid progenitor cells 47 . Similarly, GAS2 can suppress the apoptosis status and chemotherapeutic sensitivity of Jurkat, CCRF‐CEM or K562 cells 36,48 . It is noteworthy that, in leukaemia cells, GAS2 also acts as an inhibitor of calpain activity 47 .…”