Putative Breast Tumor Suppressor TACC2 Suppresses the Aggressiveness of Breast Cancer Cells through a PLCγ Pathway

Abstract

TACC2 is a member of the transforming acidic coiled-coil-containing protein family and is associated with the centrosome-spindle apparatus during cell cycling. In vivo, the TACC2 gene is expressed in various splice forms predominantly in postmitotic tissues, including heart, muscle, kidney, and brain. Recent work has shown that members of this family, including TACC2, may be involved in the progression of certain solid tumours. The aim of the current study was to identify the role of TACC2 in the TACC2-knockdown breast cancer cell lines. TACC2 expression was examined in human cancer cell lines. TACC2 was experimentally reduced expression in human breast cancer cells. The influence of TACC2 on the biological behavior of breast cancer cells was then investigated in in vitro studies. TACC2 expression showed moderate or high levels in breast cancer cell lines. The reduced expression of TACC2 significantly increased (p < 0.05) the invasive, migratory, growth and adherence properties of the human breast cancer cell lines. Furthermore, PLCγ was expressed at higher levels in TACC2 knockdown breast cancer cell lines. The increased motile pheonotype could be inhibited by the PLCγ inhibitor, which suggested TACC2 could suppress the aggressiveness of breast cancer cells through the PLCγ Pathway. This study shows that TACC2 demonstrates the ability to play a role in governing the metastatic nature of breast cancer cells. The increased motile properties could be regulated via PLCγ signaling pathway in the TACC2 knockdown breast cancer cells. This suggests that TACC2 may function as a tumor suppressor for breast cancer. The findings also suggest that TACC2 may be a potential therapeutic target. Keywords: TACC2, breast tumor suppressor, aggressiveness, PLCγ Pathway, Caenorhabditis elegans (TAC-1), Drosophila melanogaster, Xenopus laevis (Maskin), Schizosac-charomyces pombe, AZU-1, ECTACC, TACC3, AINT, ERIC1, 8p11, 10q26, MDA-MB-231, MDA-MB-436, MDA-MB-435s, MDA-MB-453, MCF-7, BT-474, BT-482, BT-549, HRT-18, HT-115, anC1, PC3, DU-145, RT112, EJ-138, SKMES-1, A549, MRC-5, A431, HUVEC, HECV, SDS-PAGE, Western Blot Analysis, Tumour Cell Growth Assay, Cell Adhesion Assay, Cell Motility Assay using Cytodex-2 Beads, Wounding Assay, Tumour Cell Invasion Assay, Immunofluorescence Staining, Statistical Analysis