Voltage-Dependent Anion Channels (VDACs), also known as mitochondrial porins, are proteins located in the mitochondrial outer membrane (OMM). In humans there are three VDAC isoforms namely VDAC1, VDAC2 and VDAC3, encoded by three different genes with high level of homology. VDACs form pores through OMM and are involved in mitochondrial metabolic and energetic functions and in apoptotic cell death [1]. VDACs exchange metabolites between cytoplasm and mitochondria and serve as anchor point for mitochondria-interacting proteins [2-3]; in particular hexokinase II (HKII) binds to VDAC in cancer cells and provides both metabolic advantage and anti-apoptotic activity [4]. With the aim to evaluate if VDACs are useful prognostic markers for hematological cancers, we analyzed, by Real time PCR, expression levels of VDACs genes in bone marrow cells derived from patients with Acute Myeloid Leukemia (AML), Multiple Myeloma (MM) at the outset of the disease and in bone marrow cells derived from healthy subjects. The results found show that patients with VDAC2 and/or VDAC1 isoforms up-regulated had poor prognosis. Moreover, VDAC3 was down regulated in all patients with poor prognosis and HKII was up-regulated in almost all samples. Although these results have been observed on a limited number of samples, they suggest that VDAC1 and VDAC2 have anti-apoptotic activity in hematological cancers and could explain cancer cells survival in patients with poor prognosis. If these results will be confirmed on a larger number of patients, expression level of VDACs could be used as prognostic marker of hematological cancers. [1] V. Shoshan-Barmatz, et al (2010) VDAC, a multi-functional mitochondrial protein regulating cell life and death. Mol. Aspects Med. 31, 227-85. [2] A. Messina, et al (2012) VDAC isoforms from mammals. Biochim Biophys Acta, 1818, 1466-1476. [3] S. Reina, et al. (2010) Swapping of the N-terminus of VDAC1 with VDAC3 restores full activity of the channel and confers anti-aging features to the cell. FEBS Letters 584, 2837-44.
Expression of VDAC (Voltage-Dependent Anion Channel) isoforms in hematological cancers
CUVIELLO, FLAVIA;SALVIA, ANTONELLA MARIA;BISACCIA, Faustino;OSTUNI, Angela
2013-01-01
Abstract
Voltage-Dependent Anion Channels (VDACs), also known as mitochondrial porins, are proteins located in the mitochondrial outer membrane (OMM). In humans there are three VDAC isoforms namely VDAC1, VDAC2 and VDAC3, encoded by three different genes with high level of homology. VDACs form pores through OMM and are involved in mitochondrial metabolic and energetic functions and in apoptotic cell death [1]. VDACs exchange metabolites between cytoplasm and mitochondria and serve as anchor point for mitochondria-interacting proteins [2-3]; in particular hexokinase II (HKII) binds to VDAC in cancer cells and provides both metabolic advantage and anti-apoptotic activity [4]. With the aim to evaluate if VDACs are useful prognostic markers for hematological cancers, we analyzed, by Real time PCR, expression levels of VDACs genes in bone marrow cells derived from patients with Acute Myeloid Leukemia (AML), Multiple Myeloma (MM) at the outset of the disease and in bone marrow cells derived from healthy subjects. The results found show that patients with VDAC2 and/or VDAC1 isoforms up-regulated had poor prognosis. Moreover, VDAC3 was down regulated in all patients with poor prognosis and HKII was up-regulated in almost all samples. Although these results have been observed on a limited number of samples, they suggest that VDAC1 and VDAC2 have anti-apoptotic activity in hematological cancers and could explain cancer cells survival in patients with poor prognosis. If these results will be confirmed on a larger number of patients, expression level of VDACs could be used as prognostic marker of hematological cancers. [1] V. Shoshan-Barmatz, et al (2010) VDAC, a multi-functional mitochondrial protein regulating cell life and death. Mol. Aspects Med. 31, 227-85. [2] A. Messina, et al (2012) VDAC isoforms from mammals. Biochim Biophys Acta, 1818, 1466-1476. [3] S. Reina, et al. (2010) Swapping of the N-terminus of VDAC1 with VDAC3 restores full activity of the channel and confers anti-aging features to the cell. FEBS Letters 584, 2837-44.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
