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the lymph nodes. Loss of expression was far greater in primary lesions with metasta-
sis than in tumours that had not metastasised. In colon cancers too, PLCD1 expres-
sion was reduced in a majority of tumour samples, but PLCγ1 showed a marked
increase (Nomoto et al., 1995). Similarly in gastric tumours, loss of PLCD1 by meth-
ylation was noticed in 16/19 gastric cancer cell lines and 61/98 primary cancers;
methylation was associated with higher tumour grade (Hu et al., 2009). Epigenetic
silencing of the gene was found in bone marrow mononuclear cells of CML patients
but not in normal adult marrow mononuclear cells (Song et al., 2012c). Promoter
methylation was encountered in just over half of breast cancer specimens and in 7/9
cell lines tested (Xiang et al., 2010).
Among biological abilities that PLCD1 seems to suppress are cell adhesion, inva-
sion and cell proliferation, which are consistent with its putative tumour suppres-
sor function. Forced expression of PLCD1 in non-expressing cells reduced MMP7
expression and brought about alterations in cytoskeletal dynamics apparently by
inactivating cofilin (Hu et al., 2009). Cofilin, a plasma membrane-associated pro-
tein, promotes actin-depolymerisation, but primarily it is an F-actin binding protein.
Its activity and subcellular localisation is regulated by phosphorylation (Bamburg,
1999). Phosphorylated inactive cofilin has been shown to inhibit cell migration
(Popow-Wozniak et al., 2012). Equally other means which would affect migration
can be visualised. The suppressor protein DLC1 interacts with and potentiates the
activity of PLCD1 (Homma and Emori, 1995). As discussed before DLC1 is a mem-
ber of a family comprising three proteins that function as Rho GTPase-activating
proteins by virtue of the GAP domain and so actively involved in the regulation of
cell proliferation, modulation of cytoskeletal dynamics and cell migration. Kawai
et al. (2004) determined the cellular distribution of p122/RhoGAP, a GTPase-
activating protein of Rho small GTPase family, which activates PLCD1. P122
co-localised with vinculin an important link to the actin cytoskeleton. Thus much
confirmatory evidence supports the role of PLCD1 in cell adhesion phenomena and
in cell migration.
PLCD1 is said to restrain cell cycle progression at G1-S transition checkpoint by
upregulating p21 expression. Suppression of cell proliferation signalling via Akt is
also a mechanism mooted for the suppressor function of PLCD1 (Fu et al., 2007). In
a couple of cell lines, cell cycle arrest at G1-S transition has been reported. FACS
(fluorescence activated cell sorter) analysis has shown accumulation of cells in
G0/G1 and a corresponding decrease in S-phase cells (Kaproth-Joslin et al., 2008).
G1 arrest has been shown to occur in a CML cell line with ectopic expression of
PLCD1 (Song et al., 2012c). Although there is consensus about G1 arrest, G2-M
arrest is said to have occurred in breast cancer cell lines (Xiang et al., 2010).
The mode of function and nature of the effects of PLCD1 on cell proliferation
need to be explored further since views contradicting cell proliferation suppression
have also been expressed. It has been claimed that C6 glioma cells siRNA-mediated
inhibition of PLCD1 actually decreased cell proliferation and FACS data have sug-
gested tardy S-phase progression and a resultant reduction in G2/M cells (Stallings
et al., 2008). Earlier, Leung et al. (2004) had claimed that overexpression of PLCD4
by transfection upregulated the expression of EGFR and erbB2 expression and led to
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