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At least 19 recordsLinked to original sources
PubMed2005

Securin is overexpressed in breast cancer.

Securin regulates sister chromatid separation during mitosis, induces bFGF-mediated angiogenesis, and securin overexpression causes in vitro transformation and in vivo tumor formation in nude mice. As estrogen administration to oophorectomized rats increased pituitary securin expression, we used immunohistochemistry to examine securin and estrogen receptor alpha (ER-alpha) expression in 90 breast tumors and 18 normal breast tissues. Breast tumor securin and ER-alpha expression were quantitated by image analysis and expressed as fold difference relative to securin expression in normal breast tissue. Low cytoplasmic securin expression was seen in the normal breast epithelium, whereas abundant cytoplasmic and nuclear securin expression was demonstrated in all 90 breast tumors. Highest securin expression was seen in brain metastatic breast tumors (4.3-fold, P<0.01), cells derived from metastatic breast cancers (6.5-fold, P<0.001), and in invasive ductal carcinoma (mean+/-s.e.: 3.8-fold, P<0.001). Highly pleomorphic (4.1-fold) or highly proliferative breast tumors (1.6-fold) exhibited high immunohistochemical securin expression compared to low-grade breast tumors (P<0.05). Northern blot analysis in 12 of the breast tumors confirmed the immunohistochemical findings demonstrating increased securin mRNA expression compared to normal breast mucosa (2.5-fold, P=0.03), with highest securin evident in invasive (3.5-fold) vs noninvasive tumors (1.9-fold, P=0.03). In addition, some tumors that exhibited high securin expression also expressed high ER-alpha levels (P<0.0001). These results demonstrate that the estrogen-induced transforming gene, securin is abundantly expressed in breast carcinoma, and is associated with the presence of metastatic spread, and lymph node invasion. We propose immunohistochemical tumor securin expression as a potential invasive marker, and novel therapeutic target in breast cancer.

Analysis of Variance↗
PubMed2002

The dual mechanism of separase regulation by securin.

BACKGROUND: Sister chromatid separation and segregation at anaphase onset are triggered by cleavage of the chromosomal cohesin complex by the protease separase. Separase is regulated by its binding partner securin in two ways: securin is required to support separase activity in anaphase; and, at the same time, securin must be destroyed via ubiquitylation before separase becomes active. The molecular mechanisms underlying this dual regulation of separase by securin are unknown. RESULTS: We show that, in budding yeast, securin supports separase localization. Separase enters the nucleus independently of securin, but securin is required and sufficient to cause accumulation of separase in the nucleus, where its known cleavage targets reside. Securin also ensures that separase gains full proteolytic activity in anaphase. We also show that securin, while present, directly inhibits the proteolytic activity of separase. Securin prevents the binding of separase to its substrates. It also hinders the separase N terminus from interacting with and possibly inducing an activating conformational change at the protease active site 150 kDa downstream at the protein's C terminus. CONCLUSIONS: Securin inhibits the proteolytic activity of separase in a 2-fold manner. While inhibiting separase, securin is able to promote nuclear accumulation of separase and help separase to become fully activated after securin's own destruction at anaphase onset.

Binding Sites↗
PubMed2006

Degradation of securin in mouse and pig oocytes is dependent on ubiquitin-proteasome pathway and is required for proteolysis of the cohesion subunit, Rec8, at the metaphase-to-anaphase transition.

Although securin/separase/cohesion pathway was reported to regulate chromosome segregation during meiotic metaphase-to-anaphase transition, little biochemical evidence was provided. We recently found that oocytes could not progress beyond meiotic metaphase when ubiquitin-proteasome pathway was inhibited, but the mechanisms remain unclear. In the present study, we investigated the quantity of securin and Rec8 protein and the localization of securin, a cohesion subunit, during oocyte meiosis providing data in support of the hypothesis that the effect of ubiquitin-proteasome pathway on metaphase-to-anaphase transition was mediated by regulating securin and Rec8 degradation in mouse and pig oocytes. In germinal vesicle-stage oocytes, immunostaining of securin was mainly localized in the germinal vesicle. Shortly after germinal vesicle breakdown, immunoreactive securin accumulated around the condensed chromosomes at prometaphase I. At metaphase I and metaphase II, when chromosomes were organized at the equatorial plate, immunoreactive securin was concentrated around the aligned chromosomes, putatively associated with the position of the metaphase spindle. The accumulation of securin could not be detected at anaphase I and anaphase II. In both mouse and pig oocytes, Western blot analysis showed that securin protein was low at germinal vesicle stage, reached the highest level at metaphase I, while decreased at anaphase I. Securin was increased again at metaphase II, while it was decreased at anaphase II. Rec8 protein was present in germinal vesicle-stage oocytes and remained until metaphase I, while it was decreased at anaphase I. Like securin, Rec8 was increased at metaphase II, while it was decreased again at anaphase II. The inhibition of the ubiquitin-proteasome pathway inhibited the decrease in securin and Rec8 at metaphase-to-anaphase transitions in both mouse and pig oocytes. Microinjection of securin antibody into MII-arrested oocytes leads to the degradation of Rec8. In conclusion, these results suggest that the proteolysis of securin is dependent on ubiquitin-proteasome pathway and is necessary for the degradation of Rec8 during meiotic metaphase-to-anaphase transitions in mouse and pig oocytes.

Anaphase↗
PubMed2002

Human securin proteolysis is controlled by the spindle checkpoint and reveals when the APC/C switches from activation by Cdc20 to Cdh1.

Progress through mitosis is controlled by the sequential destruction of key regulators including the mitotic cyclins and securin, an inhibitor of anaphase whose destruction is required for sister chromatid separation. Here we have used live cell imaging to determine the exact time when human securin is degraded in mitosis. We show that the timing of securin destruction is set by the spindle checkpoint; securin destruction begins at metaphase once the checkpoint is satisfied. Furthermore, reimposing the checkpoint rapidly inactivates securin destruction. Thus, securin and cyclin B1 destruction have very similar properties. Moreover, we find that both cyclin B1 and securin have to be degraded before sister chromatids can separate. A mutant form of securin that lacks its destruction box (D-box) is still degraded in mitosis, but now this is in anaphase. This destruction requires a KEN box in the NH2 terminus of securin and may indicate the time in mitosis when ubiquitination switches from APCCdc20 to APCCdh1. Lastly, a D-box mutant of securin that cannot be degraded in metaphase inhibits sister chromatid separation, generating a cut phenotype where one cell can inherit both copies of the genome. Thus, defects in securin destruction alter chromosome segregation and may be relevant to the development of aneuploidy in cancer.

Anaphase↗
PubMed2006

Opposing securin and p53 protein expression in the oxaliplatin-induced cytotoxicity of human colorectal cancer cells.

Oxaliplatin, a clinical anticancer drug, has been used to treat colorectal cancer. Securin and p53 have been shown to regulate the cell cycle arrest and apoptosis. However, roles of securin and p53 on the oxaliplatin-induced cytotoxicity in human colorectal cancer cells remain unclear. Treatment with 1-10 microM oxaliplatin for 24 h induced the cell death, growth inhibition, and cell cycle arrest in RKO colorectal carcinoma cells. The phospho-p53 (Ser-15), total p53, and p21 proteins were elevated by oxaliplatin in RKO cells; conversely, oxaliplatin decreased the securin protein expression. The p53-functional RKO cells were higher on the cytotoxicity and cell cycle arrest at the G1 and G2/M phases than the p53-mutational SW480 cells after treatment with oxaliplatin. Oxaliplatin inhibited the securin protein expression in the p53-functional cells but not in the p53-mutational cells. The securin-wild type cells were more sensitive than the securin-null cells on the increases of cytotoxicity and sub-G1 fractions following treatment with oxaliplatin. Nevertheless, oxaliplatin elevated the activation of p53 in both securin-wild type and securin-null cells. As a whole, it is the first time to demonstrate that oxaliplatin inhibits the securin protein expression via a p53-dependent pathway, and p53 and securin may modulate the oxaliplatin-induced cytotoxicity in human colorectal cancer cells.

Antineoplastic Agents↗
PubMed2006

Securin associates with APCCdh1 in prometaphase but its destruction is delayed by Rae1 and Nup98 until the metaphase/anaphase transition.

Precisely timed ubiquitin-mediated proteolysis of mitotic regulators by the anaphase-promoting complex (APC) governs the orderly passage of cells through mitosis. The established view is that Cdc20-activated APC (APC(Cdc20)) mediates the destruction of cyclin B and securin at the metaphase/anaphase transition, and that Cdh1-activated APC (APC(Cdh1)) has no role in this process. We recently reported that securin, but not cyclin B, is prematurely targeted for destruction by the APC in mutant mice that have low levels of the nuclear transport factors Rae1 and Nup98. We found that Rae1 and Nup98 assemble into a complex with APC(Cdh1) in prometaphase and act to delay APC(Cdh1)-mediated ubiquitination of securin until the metaphase/anaphase transition. Here we show that Rae1 and Nup98 not only form a complex with APC(Cdh1) in prometaphase but also with securin. This finding suggests that the Rae1-Nup98 complex does not inhibit early destruction of securin by preventing APC(Cdh1) from binding to securin, but by preventing ubiquitination of APC(Cdh1)-bound securin. We propose that the formation of APC(Cdh1)-securin complexes in prometaphase primes the cell for rapid securin degradation after release of the inhibitory Rae1-Nup98 complex at the metaphase/anaphase transition. We further report here that mutant mice with low levels of the Rae1-Nup98 complex are not prone to develop spontaneous tumors, despite massive aneuploidy. However, Rae1/Nup98 mutant mice are significantly more susceptible to DMBA-induced lung tumors than wild-type mice, indicating that combined Rae1/ Nup98 haplo-insufficiency does promote tumorigenesis when certain cancer-critical genes are also mutated.

Anaphase↗
PubMed2005

Depletion of securin increases arsenite-induced chromosome instability and apoptosis via a p53-independent pathway.

Arsenic is a pathologic factor of cardiovascular diseases and cancers; nevertheless, it also acts as an anticancer agent effective on acute promyelocytic leukemia and multiple myeloma. Securin, a proposed proto-oncogene, regulates cell proliferation and tumorigenesis. However, roles of securin on the arsenic-induced cell cycle arrest and apoptosis remain unknown. In this study, the effects of sodium arsenite on the expression of securin in two tissue types of cell lines, the vascular endothelial and colorectal epithelial cells, were investigated. Arsenite (8-16 microM, 24 h) increased the cytotoxicity, apoptosis, and growth inhibition in both endothelial and epithelial cells. The levels of phospho-CDC2 (threonine-161), CDC2, and cyclin B1 proteins were decreased, and the G2/M fractions were increased by arsenite. Concomitantly, arsenite markedly diminished the securin protein expression and induced the abnormal sister chromatid separation. The depletion of securin proteins increased the induction of mitotic arrest, aberrant chromosome segregation, and apoptosis after arsenite treatment. p53, a tumor suppressor protein, balances the cell survival and apoptosis. Arsenite raised the levels of phospho-p53 (serine-15) and p53 (DO-1) proteins in both the securin-wild-type and -null cells. The p53-functional cells were more susceptible than the p53-mutational cells to arsenite on the cytotoxicity and apoptosis. Besides, arsenite decreased the levels of securin proteins to a similar degree in both the p53-functional and -mutational cells. Together, it is the first time to demonstrate that the inhibition of securin expression induced by arsenite increases the chromosomal instability and apoptosis via a p53-independent pathway.

Animals↗
PubMed2002

Human securin interacts with p53 and modulates p53-mediated transcriptional activity and apoptosis.

The gene PTTG1 (encoding the pituitary tumor-transforming 1 protein) is overexpressed in several different tumor types, is tumorigenic in vivo and shows transcriptional activity. The PTTG1 protein is cell-cycle regulated and was identified as the human securin (a category of proteins involved in the regulation of sister-chromatid separation) on the basis of biochemical similarities with the Pds1p protein of budding yeast and the Cut2p protein of fission yeast. To unravel the function of human securin in oncogenesis, we carried out a phage-display screening to identify proteins that interact with securin. Notably, we isolated the p53 tumor suppressor. Pull-down and co-immunoprecipitation assays demonstrated that p53 interacts specifically with securin both in vitro and in vivo. This interaction blocks the specific binding of p53 to DNA and inhibits its transcriptional activity. Securin also inhibits the ability of p53 to induce cell death. Moreover, we observed that transfection of H1299 cells with securin induced an accumulation of G2 cells that compensated for the loss of G2 cells caused by transfection with p53. We demonstrated the physiological relevance of this interaction in PTTG1-deficient human tumor cells (PTTG1(-/-)): both apoptotic and transactivating functions of p53 were potentiated in these cells compared to parental cells. We propose that the oncogenic effect of increased expression of securin may result from modulation of p53 functions.

Apoptosis↗
PubMed2006

Securin induces genetic instability in colorectal cancer by inhibiting double-stranded DNA repair activity.

Genetic instability (GI) is a hallmark feature of tumor development. Securin, also known as pituitary tumor transforming gene (PTTG), is a mitotic checkpoint protein which is highly expressed in numerous cancers, is associated with tumor invasiveness, and induces GI in thyroid cells. We used fluorescence inter-simple sequence repeat PCR to assess GI caused primarily by DNA breakage events in 19 colorectal tumors. GI values ranged significantly, with Dukes' stage C&D colorectal tumors exhibiting greater GI and higher securin expression than Dukes' stage A&B tumors. Consistent with these findings, we observed a dose-dependent increase in GI in HCT116 cells in response to securin overexpression, as well as in non-transformed human fibroblasts. As securin has been implicated in a novel DNA repair pathway in fission yeast, we investigated its potential role in chemotoxic DNA damage response pathways in mammalian cells, using host cell reactivation assays. Securin overexpression in HCT116 cells inhibited etoposide-induced double-stranded DNA damage repair activity, and repressed Ku heterodimer function. Additionally, we observed that securin and Ku70 showed a reciprocal cytosol-nuclear translocation in response to etoposide-induced dsDNA damage. Our data suggest that, by repressing Ku70 activity and inhibiting the non-homologous end-joining dsDNA repair pathway, securin may be a critical gene in the development of GI in colorectal cancer.

Animals↗
PubMed2005

The blockage of survivin and securin expression increases the cytochalasin B-induced cell death and growth inhibition in human cancer cells.

Survivin and securin proteins are overexpressed in most cancer cells that have been shown to regulate mitotic progression. In this study, we investigated the roles of survivin and securin on cytochalasin B, a cytokinesis blocker mediating the cytotoxicity and cell growth inhibition in human cancer cells. The human lung carcinoma cell lines A549 and H1299 highly expressed survivin proteins in mitosis and concentrated on the midbodies during cytokinesis. Cytochalasin B significantly decreased cell survival, inhibited cell growth, increased the levels of G(2)/M fractions, and induced binuclei formation in lung carcinoma cells; however, the survivin proteins were concentration-dependently increased by 1 to 5 mug/ml cytochalasin B for 24 h. It is noteworthy that the expression of securin proteins was decreased in cytochalasin B-treated lung carcinoma cells. Transfection of 20 to 40 nM survivin siRNA for 48 h significantly induced the formation of multiple nuclei and apoptosis but decreased the levels of survivin and securin proteins in A549 cells. Cotreatment with survivin small interfering RNA (siRNA) and cytochalasin B increased the cytotoxicity and cell growth inhibition. In addition, the securin-null colorectal carcinoma cells were more susceptible to the cytotoxicity after cytochalasin B and survivin siRNA treatments than the securin-wild-type cells. As a whole, our results indicate that the inhibition of survivin and securin protein expression may increase the cell death and growth inhibition after cytochalasin B treatment in human cancer cells.

Cell Cycle↗
PubMed2001

Securin is not required for cellular viability, but is required for normal growth of mouse embryonic fibroblasts.

Sister chromatid separation depends on the release of cohesion by the activity of Esp1, a member of the caspase family [1, 2]. In budding yeast, Esp1p is kept inactive by its association with Pds1p, until the onset of anaphase, when Pds1p is ubiquitinated by the APC/Cdc20 complex [3--5] and subsequently degraded by the 26S proteasome. Pds1 is not an essential gene in budding yeast, but is required for cell cycle arrest prior to anaphase in response to the disruption of spindle structures [6, 7]. Thus, Pds1 mutant yeast cells display precocious sister chromatid separation in the presence of nocodazole [6]. Mammalian orthologs of yeast Esp1 and Pds1, separin and securin, have been identified [8], and, as anticipated, a nondegradable mutant form of securin inhibits sister separation when added to mitotic Xenopus egg extracts [8]. Securin was also independently identified as PTTG (pituitary tumor transforming gene), a gene overexpressed in pituitary tumors [9]. The relationship between its overexpression in tumors and its control of sister chromatid cohesion remains ill defined. To explore securin function in mammals, we took a targeted gene disruption approach in mice. Here, we report that securin is neither essential for cell viability nor required for spindle checkpoint function, and mice lacking securin are viable and apparently normal, but mouse embryonic fibroblasts lacking securin grow abnormally in culture.

Animals↗
PubMed2002

Regulation of human separase by securin binding and autocleavage.

BACKGROUND: Sister chromatid separation is initiated by separase, a protease that cleaves cohesin and thereby dissolves sister chromatid cohesion. Separase is activated by the degradation of its inhibitor securin and by the removal of inhibitory phosphates. In human cells, separase activation also coincides with the cleavage of separase, but it is not known if this reaction activates separase, which protease cleaves separase, and how separase cleavage is regulated. RESULTS: Inhibition of separase expression in human cells by RNA interference causes the formation of polyploid cells with large lobed nuclei. In mitosis, many of these cells contain abnormal chromosome plates with unseparated sister chromatids. Inhibitor binding experiments in vitro reveal that securin prevents the access of substrate analogs to the active site of separase. Upon securin degradation, the active site of full-length separase becomes accessible, allowing rapid autocatalytic cleavage of separase at one of three sites. The resulting N- and C-terminal fragments remain associated and can be reinhibited by securin. A noncleavable separase mutant retains its ability to cleave cohesin in vitro. CONCLUSIONS: Our results suggest that separase is required for sister chromatid separation during mitosis in human cells. Our data further indicate that securin inhibits separase by blocking the access of substrates to the active site of separase. Securin proteolysis allows autocatalytic processing of separase into a cleaved form, but separase cleavage is not essential for separase activation.

Amino Acid Sequence↗
PubMed2005

Securin and separase phosphorylation act redundantly to maintain sister chromatid cohesion in mammalian cells.

The spindle assembly checkpoint monitors the integrity of the spindle microtubules, which attach to sister chromatids at kinetochores and play a vital role in preserving genome stability by preventing missegregation. A key target of the spindle assembly checkpoint is securin, the separase inhibitor. In budding yeast, loss of securin results in precocious sister chromatid separation when the microtubule spindle is disrupted. However, in contrast to budding yeast, mammalian securin is not required for spindle checkpoint, suggesting that there are redundant mechanisms controlling the dissolution of sister chromatid cohesion in the absence of securin. One candidate mechanism is the inhibitory phosphorylation of separase. We generated a nonphosphorylable point mutant (S1121A) separase allele in securin-/- mouse embryonic stem cells. Securin(-/-)separase(+/S1121A) cells are viable but fail to maintain sister chromatid cohesion in response to the disruption of spindle microtubules, show enhanced sensitivity to nocodazole, and cannot recover from prometaphase arrest.

Animals↗
PubMed2001

Securin degradation is mediated by fzy and fzr, and is required for complete chromatid separation but not for cytokinesis.

We have studied the ubiquitination and degradation patterns of the human securin/PTTG protein. We show that, in contrast to budding yeast pds1, securin degradation is catalyzed by both fzy (fizzy/cdc20) and fzr (fizzy-related/cdh1/hct1). Both fzy and fzr also induce the APC/C to ubiquitinate securin in vitro. Securin degradation is mediated by an RXXL destruction box and a KEN box, and is inhibited only when both sequences are mutated. Interestingly, the non-degradable securin mutant is also partially ubiquitinated by fzy and fzr in vitro. Expressing the non-degradable securin mutant in cells frequently resulted in incomplete chromatid separation and gave rise to daughter cells connected by a thin chromatin fiber, presumably of chromosomes that failed to split completely. Strikingly, the mutant securin did not prevent the majority of sister chromatids from separating completely, nor did it prevent mitotic cyclin degradation and cytokinesis. This phenotype, reminiscent of the fission yeast cut (cells untimely torn) phenotype, is reported here for the first time in mammals.

Cdc20 Proteins↗
PubMed2005

Human full-length Securin is a natively unfolded protein.

Human Securin, also called PTTG1 (pituitary tumor transforming gene 1 product), is an estrogen-regulated proto-oncogene with multifunctional properties. We characterized human full-length Securin using a variety of biophysical techniques, such as nuclear magnetic resonance, circular dichroism, and size-exclusion chromatography. Under physiological conditions, Securin is devoid of tertiary and secondary structure except for a small amount of poly-(L-proline) type II helix and its hydrodynamic characteristics suggest it behaves as an extended polypeptide. These results suggest that Securin is unstructured in solution and so belongs to the family of natively unfolded proteins. In addition, to gain structural and quantitative insight, we investigated the binding of Securin to p53. Analytical ultracentrifugation and fluorescence anisotropy studies revealed no evidence of any direct interaction between unmodified recombinant Securin and p53 in vitro.

Humans↗
PubMed2005

Mad2 is required for inhibiting securin and cyclin B degradation following spindle depolymerisation in meiosis I mouse oocytes.

Mad2 is a pivotal component of the spindle assembly checkpoint (SAC) which inhibits anaphase promoting complex/cyclo-some (APC/C) activity by sequestering Cdc20 thereby regulating the destruction of securin and cyclin B. During mitosis, spindle depolymerisation induces a robust Mad2-dependent arrest due to inhibition of securin and cyclin B destruction. In contrast to mitosis, the molecular details underpinning the meiosis I arrest experienced by mouse oocytes exposed to spindle depolymerisation remain incompletely characterised. Notably, the role of Mad2 and the fate of the anaphase-marker, securin, are unexplored. As shown previously, we find that spindle depolymerisation by nocodazole inhibits first polar body extrusion (PBE) and stabilises cyclin B and cyclin-dependent kinase 1 activity in mouse oocytes. Here we show that stabilisation of cyclin B in nocodazole can be sustained for several hours and is associated with stabilisation of securin. These effects are SAC-mediated as, in oocytes depleted of the majority of Mad2 by morpholino antisense, securin and cyclin B are destabilised and 15% of oocytes undergo PBE. This reflects premature APC/C activation as a mutant form of cyclin B lacking its APC/C degradation signal is stable in Mad2-depleted oocytes. Moreover, homologues do not disjoin during the prolonged meiosis I arrest (> 18 h) induced by nocodaozole indicating that a non-cleavage mechanism is insufficient on its own for resolution of arm cohesion in mammalian oocytes. In conclusion, when all kinetochores lack attachment and tension, mouse oocytes mount a robust Mad2-dependent meiosis I arrest which inhibits the destruction of securin and cyclin B.

Animals↗
PubMed2005

The Rae1-Nup98 complex prevents aneuploidy by inhibiting securin degradation.

Cdc20 and Cdh1 are the activating subunits of the anaphase-promoting complex (APC), an E3 ubiquitin ligase that drives cells into anaphase by inducing degradation of cyclin B and the anaphase inhibitor securin. To prevent chromosome missegregation, APC activity directed against these mitotic regulators must be inhibited until all chromosomes are properly attached to the mitotic spindle. Here we show that in mitosis timely destruction of securin by APC is regulated by the nucleocytoplasmic transport factors Rae1 and Nup98. We show that combined Rae1 and Nup98 haploinsufficiency in mice results in premature separation of sister chromatids, severe aneuploidy and untimely degradation of securin. We find that Rae1 and Nup98 form a complex with Cdh1-activated APC (APC(Cdh1)) in early mitosis and specifically inhibit APC(Cdh1)-mediated ubiquitination of securin. Dissociation of Rae1 and Nup98 from APC(Cdh1) coincides with the release of the mitotic checkpoint protein BubR1 from Cdc20-activated APC (APC(Cdc20)) at the metaphase to anaphase transition. Together, our results suggest that Rae1 and Nup98 are temporal regulators of APC(Cdh1) that maintain euploidy by preventing unscheduled degradation of securin.

Anaphase-Promoting Complex-Cyclosome↗
PubMed2006

Securin (hPTTG1) expression is regulated by beta-catenin/TCF in human colorectal carcinoma.

Overexpression of the transcriptional activator beta-catenin, mostly owing to loss-of-function mutations of the adenomatous polyposis coli (APC) tumour suppressor gene, is crucial for the initiation and progression of human colorectal carcinogenesis. Securin is a regulator of chromosome separation and its overexpression has been shown to be involved in different tumour-promoting processes, like transformation, hyperproliferation and angiogenesis, and correlates with tumour cell invasion. However, the molecular mechanism leading to securin overexpression in human colorectal cancer is unknown. Here we show a correlated high expression of beta-catenin and securin (hPTTG1) in colorectal adenomas and carcinomas and further demonstrate that securin is a target of beta-catenin transcriptional activation. This implies that deregulation of the beta-catenin/T-cell factor-signalling pathway leads to overexpression of securin in human colorectal cancer, which subsequently may contribute to tumour progression.

Adenocarcinoma↗