The SV2 variant of KLF6 is down-regulated in hepatocellular carcinoma and displays anti-proliferative and pro-apoptotic functions

Biology of Krüppel‐like factor 6 transcriptional regulator in cell life and death

“…In addition, KLF6-SV1 and SV2 isoforms failed to transcriptionally activate p21 CIP1/WAF1 gene promoter and silencing of endogenous SV1, but not SV2, was associated with a significant reduction of cell proliferation in prostate carcinoma derived cells (17). However, it has been recently reported increased transcription of p21 CIP1/WAF1 promoter on expression of the SV2 isoform in HepG2 cells in a p53-dependent manner (40). Of particular interest, KLF6-SV1 expression was reported to be upregulated in many cancers as glioblastoma, ovarian, and lung in addition to prostate carcinoma (20).…”

“…Inhibition of KLF6-SV1 by RNAi in prostate carcinoma and ovarian cancer cell lines (41,47). v. Overexpression of KLF6-SV2 in immortalized human hepatocytes and HepG2 cell line (40).…”

“…Thus, the underlying mechanism implies the interaction between KLF-SV1 and NOXA resulting in mutual degradation, which leads to increased intracellular concentration of the prosurvival binding partner of NOXA, Mcl-1, and thereby effective blocking of apoptosis (47). Interestingly, while increased expression of the KLF6-SV1 isoform has been associated with increased cell proliferation and oncogenesis, antiproliferative and antiapoptotic functions have recently been described for the KLF6-SV2 protein variant in hepatocellular carcinoma (40).…”

Synaptic Vesicle Protein 2 (SV2) Isoforms

“…The role of SV2 in breast cells could be associated to secretory nature of mammary glands, and may interact with other vesicle proteins such as synaptobrevin, which is essential for secretion but not for the development of synaptic process (Ahnert-Hilger et al, 1996), however, the SV2 role in cancer is not clear, although it is already reported in others types of cancer, for instance, brain (de Groot et al, 2010;, pancreas (Jakobsen et al, 2002), gastrointestinal tract (Jakobsen et al, 2002;Bumming et al, 2007 ), liver (Hanoun et al, 2010), bladder (Coelho et al, 2010), prostate (Karsenty et al, 2009) and adrenals (Li et al, 1999) tumors among others, where SV2 has already been proposed as molecular and transdifferentiation marker of neural nature (Nilsson et al, 2004;Zhang et al, 2010). This is possible because in the cancerous state the terminal differentiation to the anticipated cellular type is altered and the phenomena of lineage infidelity that is associated with the ability of cancer cells to transdifferentiate, occurs in different cancer types and occur in breast cancer (Zhang et al, 2010); thus, it is a commune phenomenon that cancer cell turns-off/-on non-habitual genes changing the ontogeny to evade the immune system and hold the linage independence.…”

“…SV2 expression can have a double importance as cancer molecular marker (Zhang et al, 2010) and therapeutic use in malignity due SV2 leads the entry of BoNTA, which has anti-proliferative, pro-apoptotic and quimiodenervation functions in prostate cancer (Arnon et al, 2001;Dong et al, 2006;Choi et al, 2007;Karsenty et al, 2009;Hanoun et al, 2010;Zhenzhen et al, 2012) that could be extrapolate to breast tumors. BoNTA is recognized by SV2 receptors in neurons.…”