05 at all time points; Fig. 4C,D). Because there was a difference in apoptosis after APAP dosing in CXCR2 knockout mice versus wild-type

controls as well as differences in caspase-3 activation, we next investigated if there were differences in prosurvival protein expression after APAP administration. Western blotting for the antiapoptotic proteins cIAP2, XIAP, Bcl-2, and Bcl-XL was performed on hepatic tissues 1, 2, 4, PCI-32765 clinical trial and 6 or 8 hours after APAP administration. There were no differences in hepatic Bcl-2 or Bcl-XL expression (Fig. 5A-C). In contrast, cIAP2 expression increased in wild-type and CXCR2 knockout mice after APAP, with significant increases seen within 1 to 2 hours of APAP dosing; levels decreased to the baseline by 6 hours after APAP (Fig. 5D,E). Although significant cIAP increases were seen in wild-type and CXCR2 knockout mice with respect to control animals, there were no significant differences in cIAP levels in wild-type mice versus knockout mice at any time point. XIAP demonstrated the most significant differences in survival protein expression. Wild-type mice expressed minimal XIAP in response to APAP. In contrast, significant hepatic XIAP expression was seen after APAP in CXCR2 knockout mice (P < 0.01 at 2 and 4 hours; Fig. 5D,F). XIAP up-regulation

is controlled by activation of NF-κB p65 and p52.11, 12 To investigate if hepatic NF-κB p65 was activated in mice after APAP administration, we measured phosphorylated NF-κB p65 by immunoprecipitation and immunoblotting at various time points after APAP dosing. There was no evidence of activated 上海皓元医药股份有限公司 hepatic NF-κB p65 in wild-type or CXCR2 knockout mice after APAP Aloxistatin price (Fig. 6A). Next, we measured hepatic cytoplasmic and nuclear NF-κB p52 in knockout or wild-type mice after APAP. There was significant NF-κB p52 expression in both the cytoplasmic and nuclear hepatic proteins from CXCR2 knockout

mice treated with APAP. There was no detectable hepatic NF-κB p52 after APAP in wild-type mice (Fig. 6B-D). We examined hepatic JNK expression in wild-type and CXCR2 knockout mice after the administration of 375 mg/kg APAP to investigate whether CXCR2 signaling causes JNK activation. CXCR2 knockout and wild-type mice had a significant JNK increase after APAP. Hepatic JNK activation in wild types peaked 1 hour after APAP administration, gradually declined, and returned to the baseline at 12 hours; JNK activation in CXCR2 knockout mice was slower and weaker than that in wild-type mice (Fig. 6E,F). Less JNK activation was seen in CXCR2 knockout mice versus wild-type mice; this was statistically significant at 1 hour (P < 0.05). To determine whether the effects of CXCR2 signaling occur directly within hepatocytes rather than indirectly on other cell types within the liver, we measured CXCR2 expression on primary mouse hepatocytes; we used mouse neutrophils as a positive control because these cells are well known to express CXCR2.

05 at all time points; Fig. 4C,D). Because there was a difference in apoptosis after APAP dosing in CXCR2 knockout mice versus wild-type

controls as well as differences in caspase-3 activation, we next investigated if there were differences in prosurvival protein expression after APAP administration. Western blotting for the antiapoptotic proteins cIAP2, XIAP, Bcl-2, and Bcl-XL was performed on hepatic tissues 1, 2, 4, AZD1152-HQPA nmr and 6 or 8 hours after APAP administration. There were no differences in hepatic Bcl-2 or Bcl-XL expression (Fig. 5A-C). In contrast, cIAP2 expression increased in wild-type and CXCR2 knockout mice after APAP, with significant increases seen within 1 to 2 hours of APAP dosing; levels decreased to the baseline by 6 hours after APAP (Fig. 5D,E). Although significant cIAP increases were seen in wild-type and CXCR2 knockout mice with respect to control animals, there were no significant differences in cIAP levels in wild-type mice versus knockout mice at any time point. XIAP demonstrated the most significant differences in survival protein expression. Wild-type mice expressed minimal XIAP in response to APAP. In contrast, significant hepatic XIAP expression was seen after APAP in CXCR2 knockout mice (P < 0.01 at 2 and 4 hours; Fig. 5D,F). XIAP up-regulation

is controlled by activation of NF-κB p65 and p52.11, 12 To investigate if hepatic NF-κB p65 was activated in mice after APAP administration, we measured phosphorylated NF-κB p65 by immunoprecipitation and immunoblotting at various time points after APAP dosing. There was no evidence of activated 上海皓元医药股份有限公司 hepatic NF-κB p65 in wild-type or CXCR2 knockout mice after APAP LY2157299 cost (Fig. 6A). Next, we measured hepatic cytoplasmic and nuclear NF-κB p52 in knockout or wild-type mice after APAP. There was significant NF-κB p52 expression in both the cytoplasmic and nuclear hepatic proteins from CXCR2 knockout

mice treated with APAP. There was no detectable hepatic NF-κB p52 after APAP in wild-type mice (Fig. 6B-D). We examined hepatic JNK expression in wild-type and CXCR2 knockout mice after the administration of 375 mg/kg APAP to investigate whether CXCR2 signaling causes JNK activation. CXCR2 knockout and wild-type mice had a significant JNK increase after APAP. Hepatic JNK activation in wild types peaked 1 hour after APAP administration, gradually declined, and returned to the baseline at 12 hours; JNK activation in CXCR2 knockout mice was slower and weaker than that in wild-type mice (Fig. 6E,F). Less JNK activation was seen in CXCR2 knockout mice versus wild-type mice; this was statistically significant at 1 hour (P < 0.05). To determine whether the effects of CXCR2 signaling occur directly within hepatocytes rather than indirectly on other cell types within the liver, we measured CXCR2 expression on primary mouse hepatocytes; we used mouse neutrophils as a positive control because these cells are well known to express CXCR2.

“
“We tested how the availability of carbon and nitrogen determines both the production of Asparagopsis taxiformis (Delile) V. Trevis. and content of the two major halocarbons, bromoform and dibromoacetic acid. The halogenated secondary metabolites

of Asparagopsis species Caspase activation are particularly interesting from an applied perspective due to their remarkable antimicrobial activity. Terrestrial ecologists named the relationship between resources and secondary metabolites as the carbon (C)/nutrient balance (CNB) hypothesis. This relationship was tested both in the laboratory, with a factorial analysis using different concentrations of total ammonia (TAN) and dissolved inorganic carbon (DIC), and in an integrated aquaculture system where TAN and Selleckchem MK1775 DIC fluxes of fish effluent were manipulated.

The total C/N content of A. taxiformis biomass cultivated in laboratory was highly significantly linearly related to the content of both halocarbons, as predicted by the CNB hypothesis. A. taxiformis cultivated at low levels of carbon and high levels of nitrogen (N) (lowest C/N ratio) had the lowest content in both halogenated metabolites. Increased availability of CO2 in the medium resulted in a general higher halocarbon content in the biomass, even though the effect was only statistically significant for bromoform at high levels of N. The farm experiments

supported the results of the laboratory experiments. DIC fluxes had the highest effect on the production of both bromoform and biomass, as shown by multiple regression analysis. In A. taxiformis integrated aquaculture, C, rather than N, is the most important factor affecting the production of biomass and of valuable halocarbon secondary metabolites. “
“The brown algal genus medchemexpress Padina (Dictyotales, Phaeophyceae) is distributed worldwide in tropical and temperate seas. Global species diversity and distribution ranges, however, remain largely unknown. Species-level diversity was reassessed using DNA-based, algorithmic species delineation techniques based on cox3 and rbcL sequence data from 221 specimens collected worldwide. This resulted in estimates ranging from 39 to 61 putative species (ESUs), depending on the technique as well as the locus. We discuss the merits, potential pitfalls, and evolutionary and biogeographic significance of algorithmic species delineation. We unveil patterns whereby ESUs are in all but one case restricted to either the Atlantic or Indo-Pacific Ocean. Within ocean basins we find evidence for the vast majority of ESUs to be confined to a single marine realm. Exceptions, whereby ESUs span up to three realms, are located in the Indo-Pacific Ocean.

“
“We tested how the availability of carbon and nitrogen determines both the production of Asparagopsis taxiformis (Delile) V. Trevis. and content of the two major halocarbons, bromoform and dibromoacetic acid. The halogenated secondary metabolites

of Asparagopsis species learn more are particularly interesting from an applied perspective due to their remarkable antimicrobial activity. Terrestrial ecologists named the relationship between resources and secondary metabolites as the carbon (C)/nutrient balance (CNB) hypothesis. This relationship was tested both in the laboratory, with a factorial analysis using different concentrations of total ammonia (TAN) and dissolved inorganic carbon (DIC), and in an integrated aquaculture system where TAN and MK-2206 supplier DIC fluxes of fish effluent were manipulated.

The total C/N content of A. taxiformis biomass cultivated in laboratory was highly significantly linearly related to the content of both halocarbons, as predicted by the CNB hypothesis. A. taxiformis cultivated at low levels of carbon and high levels of nitrogen (N) (lowest C/N ratio) had the lowest content in both halogenated metabolites. Increased availability of CO2 in the medium resulted in a general higher halocarbon content in the biomass, even though the effect was only statistically significant for bromoform at high levels of N. The farm experiments

supported the results of the laboratory experiments. DIC fluxes had the highest effect on the production of both bromoform and biomass, as shown by multiple regression analysis. In A. taxiformis integrated aquaculture, C, rather than N, is the most important factor affecting the production of biomass and of valuable halocarbon secondary metabolites. “
“The brown algal genus medchemexpress Padina (Dictyotales, Phaeophyceae) is distributed worldwide in tropical and temperate seas. Global species diversity and distribution ranges, however, remain largely unknown. Species-level diversity was reassessed using DNA-based, algorithmic species delineation techniques based on cox3 and rbcL sequence data from 221 specimens collected worldwide. This resulted in estimates ranging from 39 to 61 putative species (ESUs), depending on the technique as well as the locus. We discuss the merits, potential pitfalls, and evolutionary and biogeographic significance of algorithmic species delineation. We unveil patterns whereby ESUs are in all but one case restricted to either the Atlantic or Indo-Pacific Ocean. Within ocean basins we find evidence for the vast majority of ESUs to be confined to a single marine realm. Exceptions, whereby ESUs span up to three realms, are located in the Indo-Pacific Ocean.

Transforming growth factor beta (TGF-β) signals through intermediary SMAD proteins, which

activate differentiation programs and inhibit cell-cycle progression during early carcinogenesis.38 In TISC-driven hepatocarcinogenesis, the loss Cobimetinib datasheet of intermediary regulators, such as β2-Spectrin, results in the malignant transformation of liver stem and progenitor cells to TISCs via loss of differentiation and growth-arrest signals (Fig. 1).39 Within liver TISC populations, increased expression of ESC transcription factors Oct4 and Nanog, driven by loss of TGF-β differentiation signals, propagates self-renewal characteristics. Small molecule promoters of TGF-β signaling, which may restore growth-arrest and differentiation signals in TISCs, have been proposed as a TISC-targeting strategy. In related work, targeting of the fifth subunit of the COP9 signalosome (CSN5), which is functionally buy R788 interconnected with TGF-β signaling, resulted in decreased tumor growth of human HCC cell lines in vivo.40 Because chronic hepatitis C virus (HCV) infection is the primary cause of HCC in the United States, murine models of HCV-induced HCC are highly relevant. In HCV core+ or NS5A+ transgenic mice, up-regulation of Toll-like receptor-4 (TLR4)

expression during HCV-induced chronic injury was associated with impaired TGF-β signaling, up-regulated Nanog expression, and increased malignant potential, a process that is exacerbated by a high-fat diet.41, 42 TLR4 activation occurred predominantly in Nanog-dependent

CD133+CD49f+ TISCs. Targeting Nanog directly in these TISCs results in decreased tumor initiation, by down-regulating cellular growth regulators. TLR4-initiated and Nanog-dependent activation of yes-associated protein 1 (YAP1), a regulator of Hippo signaling, results in inhibition of TGF-β through suppression of nuclear translocation of SMAD3. Silencing Yap1 results in suppression of Nanog transcription, restoration of TGF-β/SMAD3 signaling, and sensitization of TISCs to rapamycin and sorafenib. Canonical β-catenin signaling through activation of TCF/LEF promoters is a general mechanism of stem cell function, resulting in stem cell proliferation, survival, and MCE公司 inhibition of differentiation. Mutations in β-catenin and related complex proteins often result in β-catenin activation without Wnt initiation.43 Although β-catenin mutations are well characterized in HCC, mutations that protect β-catenin from degradation are not, by themselves, sufficient to induce HCC in murine models.43, 44 β-catenin activation is also found in normal LPCs, proliferating in response to chronic liver injury. Conversely, in liver-specific β-catenin knockout mice, LPC proliferation is reduced in response to the DDC diet.

Transforming growth factor beta (TGF-β) signals through intermediary SMAD proteins, which

activate differentiation programs and inhibit cell-cycle progression during early carcinogenesis.38 In TISC-driven hepatocarcinogenesis, the loss find more of intermediary regulators, such as β2-Spectrin, results in the malignant transformation of liver stem and progenitor cells to TISCs via loss of differentiation and growth-arrest signals (Fig. 1).39 Within liver TISC populations, increased expression of ESC transcription factors Oct4 and Nanog, driven by loss of TGF-β differentiation signals, propagates self-renewal characteristics. Small molecule promoters of TGF-β signaling, which may restore growth-arrest and differentiation signals in TISCs, have been proposed as a TISC-targeting strategy. In related work, targeting of the fifth subunit of the COP9 signalosome (CSN5), which is functionally Transmembrane Transproters modulator interconnected with TGF-β signaling, resulted in decreased tumor growth of human HCC cell lines in vivo.40 Because chronic hepatitis C virus (HCV) infection is the primary cause of HCC in the United States, murine models of HCV-induced HCC are highly relevant. In HCV core+ or NS5A+ transgenic mice, up-regulation of Toll-like receptor-4 (TLR4)

expression during HCV-induced chronic injury was associated with impaired TGF-β signaling, up-regulated Nanog expression, and increased malignant potential, a process that is exacerbated by a high-fat diet.41, 42 TLR4 activation occurred predominantly in Nanog-dependent

CD133+CD49f+ TISCs. Targeting Nanog directly in these TISCs results in decreased tumor initiation, by down-regulating cellular growth regulators. TLR4-initiated and Nanog-dependent activation of yes-associated protein 1 (YAP1), a regulator of Hippo signaling, results in inhibition of TGF-β through suppression of nuclear translocation of SMAD3. Silencing Yap1 results in suppression of Nanog transcription, restoration of TGF-β/SMAD3 signaling, and sensitization of TISCs to rapamycin and sorafenib. Canonical β-catenin signaling through activation of TCF/LEF promoters is a general mechanism of stem cell function, resulting in stem cell proliferation, survival, and MCE公司 inhibition of differentiation. Mutations in β-catenin and related complex proteins often result in β-catenin activation without Wnt initiation.43 Although β-catenin mutations are well characterized in HCC, mutations that protect β-catenin from degradation are not, by themselves, sufficient to induce HCC in murine models.43, 44 β-catenin activation is also found in normal LPCs, proliferating in response to chronic liver injury. Conversely, in liver-specific β-catenin knockout mice, LPC proliferation is reduced in response to the DDC diet.

Transforming growth factor beta (TGF-β) signals through intermediary SMAD proteins, which

activate differentiation programs and inhibit cell-cycle progression during early carcinogenesis.38 In TISC-driven hepatocarcinogenesis, the loss Alectinib purchase of intermediary regulators, such as β2-Spectrin, results in the malignant transformation of liver stem and progenitor cells to TISCs via loss of differentiation and growth-arrest signals (Fig. 1).39 Within liver TISC populations, increased expression of ESC transcription factors Oct4 and Nanog, driven by loss of TGF-β differentiation signals, propagates self-renewal characteristics. Small molecule promoters of TGF-β signaling, which may restore growth-arrest and differentiation signals in TISCs, have been proposed as a TISC-targeting strategy. In related work, targeting of the fifth subunit of the COP9 signalosome (CSN5), which is functionally PS-341 clinical trial interconnected with TGF-β signaling, resulted in decreased tumor growth of human HCC cell lines in vivo.40 Because chronic hepatitis C virus (HCV) infection is the primary cause of HCC in the United States, murine models of HCV-induced HCC are highly relevant. In HCV core+ or NS5A+ transgenic mice, up-regulation of Toll-like receptor-4 (TLR4)

expression during HCV-induced chronic injury was associated with impaired TGF-β signaling, up-regulated Nanog expression, and increased malignant potential, a process that is exacerbated by a high-fat diet.41, 42 TLR4 activation occurred predominantly in Nanog-dependent

CD133+CD49f+ TISCs. Targeting Nanog directly in these TISCs results in decreased tumor initiation, by down-regulating cellular growth regulators. TLR4-initiated and Nanog-dependent activation of yes-associated protein 1 (YAP1), a regulator of Hippo signaling, results in inhibition of TGF-β through suppression of nuclear translocation of SMAD3. Silencing Yap1 results in suppression of Nanog transcription, restoration of TGF-β/SMAD3 signaling, and sensitization of TISCs to rapamycin and sorafenib. Canonical β-catenin signaling through activation of TCF/LEF promoters is a general mechanism of stem cell function, resulting in stem cell proliferation, survival, and MCE公司 inhibition of differentiation. Mutations in β-catenin and related complex proteins often result in β-catenin activation without Wnt initiation.43 Although β-catenin mutations are well characterized in HCC, mutations that protect β-catenin from degradation are not, by themselves, sufficient to induce HCC in murine models.43, 44 β-catenin activation is also found in normal LPCs, proliferating in response to chronic liver injury. Conversely, in liver-specific β-catenin knockout mice, LPC proliferation is reduced in response to the DDC diet.

The prognosis is very poor for patients selleck inhibitor who have unresectable tumors, with a median survival of approximately 6 months.2 At present, even the most effective forms of systemic therapy, such as doxorubicin1, 3 or sorafenib,2, 4 only minimally extend the lifespan of these patients. Therefore, a thorough

understanding of the underlying mechanisms regarding tumor growth and metastasis is vital for the development of efficacious therapeutics. Sirtuins are mammalian homologs of the yeast silent information regulator 2 (SIR2), which are histone deacetylases that utilizes nicotinamide adenine dinucleotide as a cofactor for their functions.5 The yeast, SIR2, regulates aging by maintaining transcriptional silencing of the mating-type loci, the ribosomal DNA locus, and the telomeres.6 In mammals, there are seven homologs of SIR2 (SIRT1-7), of which SIRT1 is considered to be the human ortholog of SIR2.7 SIRT1 is mainly localized to the nucleus and plays a key role in energy metabolism, telomeric maintenance,

and genomic stability by targeting a variety of nonhistone proteins.8-11 The role of SIRT1 in cancer is controversial because it may act as a tumor promoter or suppressor, depending on the tumor type.12 SIRT2 acts on certain substrates of SIRT1, such as H4K16, p53, FOXO3, and p65.13-16 Nevertheless, the predominant cytoplasmic localization of SIRT2 and its role in the regulation MCE of tubulin dynamics and neuronal motility suggested that it might have Pexidartinib order functional roles distinctive from SIRT1.17, 18 Indeed, recent findings suggested that SIRT2 is associated

with mitotic apparatus during the cell cycle19, 20 and is essential for maintaining genomic stability by deacetylating CDH1 and CDC20 of the anaphase-promoting complex/cyclosome.21 Emerging evidence has also suggested that SIRT2 is involved in tumorigenesis.21 SIRT2 deficiency results in aneuploidy and mitotic cell death, and SIRT2-deficient mice have a higher propensity for developing tumors.21 Moreover, SIRT2 expression is down-regulated in some cancers,21, 22 suggestive of a tumor-suppressor function. SIRT1 expression is up-regulated in HCC, and SIRT1 may play a role in HCC tumorigenesis through telomere maintenance.23 In this study, we showed that SIRT2 is also up-regulated in HCC. Overexpression of SIRT2 in primary HCC tumors is positively correlated with microscopic vascular invasion and adverse patient prognosis. Using HCC cell models, we uncovered a key role of SIRT2 as a tumor promoter in HCC by promoting epithelial-mesenchymal transition (EMT) and motility of HCC cells by targeting the protein kinase B/glycogen synthase kinase (Akt/GSK)3-β/β-catenin-signaling pathway. Our findings provide a rationale for the clinical exploration of the use of sirtuin inhibitors in HCC therapy.

The prognosis is very poor for patients selleck compound who have unresectable tumors, with a median survival of approximately 6 months.2 At present, even the most effective forms of systemic therapy, such as doxorubicin1, 3 or sorafenib,2, 4 only minimally extend the lifespan of these patients. Therefore, a thorough

understanding of the underlying mechanisms regarding tumor growth and metastasis is vital for the development of efficacious therapeutics. Sirtuins are mammalian homologs of the yeast silent information regulator 2 (SIR2), which are histone deacetylases that utilizes nicotinamide adenine dinucleotide as a cofactor for their functions.5 The yeast, SIR2, regulates aging by maintaining transcriptional silencing of the mating-type loci, the ribosomal DNA locus, and the telomeres.6 In mammals, there are seven homologs of SIR2 (SIRT1-7), of which SIRT1 is considered to be the human ortholog of SIR2.7 SIRT1 is mainly localized to the nucleus and plays a key role in energy metabolism, telomeric maintenance,

and genomic stability by targeting a variety of nonhistone proteins.8-11 The role of SIRT1 in cancer is controversial because it may act as a tumor promoter or suppressor, depending on the tumor type.12 SIRT2 acts on certain substrates of SIRT1, such as H4K16, p53, FOXO3, and p65.13-16 Nevertheless, the predominant cytoplasmic localization of SIRT2 and its role in the regulation MCE of tubulin dynamics and neuronal motility suggested that it might have Carfilzomib functional roles distinctive from SIRT1.17, 18 Indeed, recent findings suggested that SIRT2 is associated

with mitotic apparatus during the cell cycle19, 20 and is essential for maintaining genomic stability by deacetylating CDH1 and CDC20 of the anaphase-promoting complex/cyclosome.21 Emerging evidence has also suggested that SIRT2 is involved in tumorigenesis.21 SIRT2 deficiency results in aneuploidy and mitotic cell death, and SIRT2-deficient mice have a higher propensity for developing tumors.21 Moreover, SIRT2 expression is down-regulated in some cancers,21, 22 suggestive of a tumor-suppressor function. SIRT1 expression is up-regulated in HCC, and SIRT1 may play a role in HCC tumorigenesis through telomere maintenance.23 In this study, we showed that SIRT2 is also up-regulated in HCC. Overexpression of SIRT2 in primary HCC tumors is positively correlated with microscopic vascular invasion and adverse patient prognosis. Using HCC cell models, we uncovered a key role of SIRT2 as a tumor promoter in HCC by promoting epithelial-mesenchymal transition (EMT) and motility of HCC cells by targeting the protein kinase B/glycogen synthase kinase (Akt/GSK)3-β/β-catenin-signaling pathway. Our findings provide a rationale for the clinical exploration of the use of sirtuin inhibitors in HCC therapy.

The prognosis is very poor for patients DAPT who have unresectable tumors, with a median survival of approximately 6 months.2 At present, even the most effective forms of systemic therapy, such as doxorubicin1, 3 or sorafenib,2, 4 only minimally extend the lifespan of these patients. Therefore, a thorough

understanding of the underlying mechanisms regarding tumor growth and metastasis is vital for the development of efficacious therapeutics. Sirtuins are mammalian homologs of the yeast silent information regulator 2 (SIR2), which are histone deacetylases that utilizes nicotinamide adenine dinucleotide as a cofactor for their functions.5 The yeast, SIR2, regulates aging by maintaining transcriptional silencing of the mating-type loci, the ribosomal DNA locus, and the telomeres.6 In mammals, there are seven homologs of SIR2 (SIRT1-7), of which SIRT1 is considered to be the human ortholog of SIR2.7 SIRT1 is mainly localized to the nucleus and plays a key role in energy metabolism, telomeric maintenance,

and genomic stability by targeting a variety of nonhistone proteins.8-11 The role of SIRT1 in cancer is controversial because it may act as a tumor promoter or suppressor, depending on the tumor type.12 SIRT2 acts on certain substrates of SIRT1, such as H4K16, p53, FOXO3, and p65.13-16 Nevertheless, the predominant cytoplasmic localization of SIRT2 and its role in the regulation 上海皓元医药股份有限公司 of tubulin dynamics and neuronal motility suggested that it might have Dabrafenib nmr functional roles distinctive from SIRT1.17, 18 Indeed, recent findings suggested that SIRT2 is associated

with mitotic apparatus during the cell cycle19, 20 and is essential for maintaining genomic stability by deacetylating CDH1 and CDC20 of the anaphase-promoting complex/cyclosome.21 Emerging evidence has also suggested that SIRT2 is involved in tumorigenesis.21 SIRT2 deficiency results in aneuploidy and mitotic cell death, and SIRT2-deficient mice have a higher propensity for developing tumors.21 Moreover, SIRT2 expression is down-regulated in some cancers,21, 22 suggestive of a tumor-suppressor function. SIRT1 expression is up-regulated in HCC, and SIRT1 may play a role in HCC tumorigenesis through telomere maintenance.23 In this study, we showed that SIRT2 is also up-regulated in HCC. Overexpression of SIRT2 in primary HCC tumors is positively correlated with microscopic vascular invasion and adverse patient prognosis. Using HCC cell models, we uncovered a key role of SIRT2 as a tumor promoter in HCC by promoting epithelial-mesenchymal transition (EMT) and motility of HCC cells by targeting the protein kinase B/glycogen synthase kinase (Akt/GSK)3-β/β-catenin-signaling pathway. Our findings provide a rationale for the clinical exploration of the use of sirtuin inhibitors in HCC therapy.