Upregulation of SPRR3 Promotes Colorectal Tumorigenesis

Cho, Dong‐Hyung; Jo, Yoon Kyung; Roh, Seon Ae; Na, Young-Soon; Kim, Tae Won; Jang, Se Jin; Kim, Yong‐Sung; Kim, Jin Cheon

doi:10.2119/molmed.2009.00187

Cited by 36 publications

(42 citation statements)

References 33 publications

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“…A correlation between SPRR3 and a specific molecular pathway connecting Wnt and RAS pathways has been demonstrated from gene expression profiles of sporadic colorectal cancers (CRCs) [13]. Extension of this study demonstrated that SPRR3 overexpression accelerates CRC cell proliferation and p53 downregulation, and may be associated with colorectal tumorigenesis [14].…”

Section: Introductionmentioning

confidence: 70%

“…Loss of SPRR3 is suggested to be a harbinger of early esophageal malignant transformation, and observation of its downregulation may be valuable in diagnosis and assessment of response to chemoradiotherapy in esophageal squamous cell cancer (ESCC) [16][17][18]. In contrast to the pattern seen in ESCC, in CRC SPRR3 overexpression not only causes accelerated tumor cell proliferation but it is also associated with lymphovascular invasion [14]. Interestingly, in the current study SPRR3 overexpression was closely correlated with less advanced stages and the absence of lymph node metastasis in BC patients; however, there was no correlation with incidence of recurrence or survival duration.…”

Section: Discussionmentioning

confidence: 99%

“…SPRR3 cDNA PCR-amplified and subcloned into hemagglutinin (HA)-tagged pcDNA3 (pHA-SPRR3) (Invitrogen) was used to generate stable transfectants, as previously described [14]. T-47D cells were transfected with pHA-SPRR3 using lipofectamine 2000 (Invitrogen).…”

Section: Cell Line Transfection and Proliferation Assaymentioning

confidence: 99%

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Expression of SPRR3 is associated with tumor cell proliferation in less advanced stages of breast cancer

Kim

Cho

et al. 2011

Breast Cancer Res Treat

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Small proline rich repeat protein 3 (SPRR3), a member of the SPRR family of cornified envelope precursor proteins, is a marker for terminal squamous cell differentiation. Previously, this laboratory showed that SPRR3 is strongly upregulated in colorectal tumors, and is involved in the tumorigenesis. The current study was performed to investigate the expression status and effect of SPRR3 in breast cancers (BCs). SPRR3 expression was examined by immunohistochemistry in 241 tumor samples from BC patients. SPRR3 was overexpressed in more than half of all BC samples. SPRR3 overexpression was significantly associated with less advanced stage (0-1 vs. II-III) and the absence of lymph node metastasis (P = 0.004 and 0.013, respectively). HER2/neu overexpression was closely correlated with SPRR3 overexpression in a multivariate analysis (OR, 3.23, P = 0.017). To assess the influence of SPRR3 on cell proliferation and related signaling pathways, SPRR3-transfected clones from the SPRR3-negative T-47D human BC cell line were generated. Among the total of six SPRR3-overexpressing clones, five showed marked proliferation compared with SPRR3-nonexpressing control cells from day 3 of culture (P < 0.001). The SPRR3-overexpressing BC clones showed increased phosphorylation of AKT and MDM2, p21 overexpression, and p53 downregulation. Furthermore, phosphorylation of MEK and MAPK was markedly increased. This study demonstrates that SPRR3 promotes BC cell proliferation by enhancing p53 degradation via the AKT and MAPK pathways and is, therefore, a potential novel therapeutic target for less advanced stages of BC.

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Section: Introductionmentioning

confidence: 70%

Section: Discussionmentioning

confidence: 99%

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Expression of SPRR3 is associated with tumor cell proliferation in less advanced stages of breast cancer

Kim

Cho

et al. 2011

Breast Cancer Res Treat

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“…SPRR-v1 is highly expressed in the esophageal mucosa of healthy individuals, whereas SPRR3-v2 expression is higher in the adjacent mucosal tissues in patients with esophageal squamous cell carcinoma [21]. High SPRR3 expression also has been reported in colorectal cancer, breast cancer, and glioblastoma multiforme (the most common primary brain tumor in adults); thus, this protein is a reported candidate biomarker for cancer diagnosis [22][23][24].…”

Section: Discussionmentioning

confidence: 99%

Identification and evaluation of potential forensic marker proteins in vaginal fluid by liquid chromatography/mass spectrometry

2015

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Vaginal fluid is one of the most common body fluids found at crime scenes. Discriminating vaginal fluid from other body fluids is important in forensic science; however, few potential protein markers have been reported to date. Proteomic methods for identifying protein markers have gained attention, although few reports have applied this technology to forensic protein markers. Therefore, to identify characteristic vaginal proteins, we examined various body fluids (nasal secretions, saliva, urine, semen, vaginal fluids, and sweat) using liquid chromatography/electrospray ionization time-of-flight mass spectrometry and peptide mass fingerprinting. We identified three components (average molecular mass values 17,237 ± 2, 18,063 ± 2, and 15,075 ± 1) detectable only in vaginal samples: two human small proline-rich protein 3 (SPRR3) isoforms and a human fatty acid-binding protein 5 (FABP5) with an acetylated (+42) N-terminal region lacking the initiator methionine residue (-131). Using ELISA, these yielded markedly high average values in vaginal fluids. The mass spectra of these proteins were not detected in infant saliva but were detected in the vaginal fluid throughout the menstrual cycle. The results of forensic analysis (detection limit, mixed body fluid samples, casework samples, and blind samples) suggest that these proteins are potential forensic markers. In conclusion, high SPRR3 and FABP5 expression levels, which may be used as potential markers for vaginal fluid identification in forensic science, were detected in vaginal fluids from healthy adults.

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“…SPRRs are primarily expressed in cornified envelope and stratified epithelium such as skin and, in the case of SPRR3, foregut and esophagus 6 . Interestingly, some studies have shown that SPRR3 is also associated with pro-survival functions in colorectal cancer 7 . However, the mechanism by which SPRR3 promotes cell survival remains undetermined.…”

Section: Introductionmentioning

confidence: 99%

Identification of Small Proline-Rich Repeat Protein 3 as a Novel Atheroprotective Factor That Promotes Adaptive Akt Signaling in Vascular Smooth Muscle Cells

Segedy

Pyle

et al. 2014

ATVB

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Objective Atherosclerosis is the primary driver of cardiovascular disease, the leading cause of death worldwide. Identification of naturally occurring atheroprotective genes has become a major goal for development of interventions that will limit atheroma progression and associated adverse events. To this end, we have identified SPRR3 (small proline-rich repeat protein 3) as selectively upregulated in vascular smooth muscle cells (VSMCs) of atheroma-bearing arterial tissue versus healthy arterial tissue. In this study, we sought to determine the role of SPRR3 in atheroma pathophysiology. Approach and Results We found that atheroprone ApoE-null mice lacking SPRR3 developed significantly greater atheroma burden. To determine the cellular driver(s) of this increase, we evaluated SPRR3-dependent changes in bone-marrow-derived cells, endothelial cells (ECs), and VSMCs. Bone marrow transplant of SPRR3-expressing cells into SPRR3−/− ApoE−/− recipients failed to rescue atheroma burden. Similarly, ECs did not exhibit a response to SPRR3 loss. However, atheromas from SPRR3-deficient mice exhibited increased TUNEL-positive VSMCs compared with control. Cell death in SPRR3-deficient VSMCs was significantly increased in vitro. Conversely, SPRR3-overexpressing VSMCs exhibited reduced apoptosis compared with control. We also observed a PI3K/Akt-dependent positive association between SPRR3 expression and levels of active Akt in VSMCs. The survival advantage seen in SPRR3-overexpressing VSMCs was abrogated following the addition of a PI3K/Akt pathway inhibitor. Conclusions These results indicate that SPRR3 protects the lesion from VSMC loss by promoting survival signaling in plaque VSMCs, thereby significantly decreasing atherosclerosis progression. As the first identified atheroma-specific VSMC pro-survival factor, SPRR3 represents a potential target for lesion-specific modulation of VSMC survival.

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Upregulation of SPRR3 Promotes Colorectal Tumorigenesis

Cited by 36 publications

References 33 publications

Expression of SPRR3 is associated with tumor cell proliferation in less advanced stages of breast cancer

Expression of SPRR3 is associated with tumor cell proliferation in less advanced stages of breast cancer

Identification and evaluation of potential forensic marker proteins in vaginal fluid by liquid chromatography/mass spectrometry

Identification of Small Proline-Rich Repeat Protein 3 as a Novel Atheroprotective Factor That Promotes Adaptive Akt Signaling in Vascular Smooth Muscle Cells

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