Epigenetic silencing of<i>SMOC1</i>in traditional serrated adenoma and colorectal cancer

Aoki, Hironori; Yamamoto, Eiko; Takasawa, Akira; Niinuma, Takeshi; Yamano, Hiro‐o; Harada, Taku; Matsushita, Hirokazu; Yoshikawa, Kenjiro; Takagi, Ryo; Harada, Eiji; Tanaka, Yoshihito; Yoshida, Yuko; Aoyama, Tomoyuki; Eizuka, Makoto; Yorozu, Akira; Kitajima, Hiroshi; Kai, Masahiro; Sawada, Norimasa; Sugai, Tamotsu; Nakase, Hiroshi; Suzuki, Hiromu

doi:10.18632/oncotarget.23523

Cited by 26 publications

(34 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our immunohistochemical analysis revealed that SMOC1 expression is reduced in TSAs, whereas it is abundantly expressed in normal colon and SSA/Ps [15]. This suggests that SMOC1 could be a useful marker for discriminating SSA/Ps from TSAs.…”

Section: Epigenetic Silencing Of Secreted Protein Acidic and Rich In mentioning

confidence: 65%

“…Analysis using CRC cell lines showed that SMOC1 methylation is associated with gene silencing, and ectopic expression of SMOC1 suppressed CRC cell proliferation and xenograft formation in nude mice, which is indicative of its tumor suppressor function. Collectively, these results suggest that SMOC1 methylation may play a key role in the development of TSAs and adenomas that could progress to CIMP-low CRCs [15].…”

Section: Epigenetic Silencing Of Secreted Protein Acidic and Rich In mentioning

confidence: 77%

“…When we further analyzed SMOC1 methylation in a large number of clinical specimens, we found that SMOC1 was also frequently methylated in conventional adenomas and CRCs [15]. For non-invasive tumors, SMOC1 methylation was positively associated with older age, larger tumor size, KRAS mutation, TP53 mutation, and CIMP-low.…”

Section: Epigenetic Silencing Of Secreted Protein Acidic and Rich In mentioning

confidence: 92%

“…To identify DNA methylation associated with the TSA development, we analyzed a series of TSAs containing both protruding and flat components within the same tumors [15] (Fig. 3).…”

Section: Epigenetic Silencing Of Secreted Protein Acidic and Rich In mentioning

confidence: 99%

“…SMOC1 belongs to the SPARC family of matricellular proteins, which has 8 known members: SPARC, SPARCL1/Hevin, SPOCK1, -2, -3, SMOC1, -2 and FSTL1. Although the biological function of SMOC1 is not fully understood, it is reportedly associated with osteoblast differentiation, ocular and limb development, and angiogenesis [15][16][17]. Members of SPARC family have been implicated in various tumor types.…”

Section: Epigenetic Silencing Of Secreted Protein Acidic and Rich In mentioning

confidence: 99%

See 4 more Smart Citations

Integrated Analysis of the Endoscopic, Pathological and Molecular Characteristics of Colorectal Tumorigenesis

et al. 2018

Self Cite

View full text Add to dashboard Cite

Background: Colorectal cancers (CRCs) develop through the accumulation of genetic and epigenetic alterations of oncogenes and tumor suppressor genes. In addition to the well-characterized adenoma-carcinoma sequence, the serrated neoplasia pathway is now recognized as an alternative pathway for CRC development. Summary: Through analysis of the colonoscopic, pathological, and molecular features of colorectal tumors, we identified a novel microsurface structure characteristic of serrated lesions. The Type II-Open (Type II-O) pit pattern is highly specific to sessile serrated adenoma/polyps (SSA/Ps), and Type-II-O-positive tumors frequently exhibit v-raf murine sarcoma viral oncogene homolog B1 (BRAF) mutation and 5′-C-phosphate-G-3′ (CpG) island hypermethylation. By screening DNA methylation associated with the development of serrated lesions, we detected methylation of secreted protein acidic and rich in cysteine (SPARC)-related modular calcium binding 1 (SMOC1) in traditional serrated adenomas (TSAs). Epigenetic silencing of SMOC1 is prevalent among TSAs but it is rarely observed in SSA/Ps, which suggests SMOC1 could be a useful diagnostic marker of serrated lesions. We also searched for epigenetic alterations associated with the growth pattern of colorectal tumors and found that methylation of neurotensin receptor 1 is associated with lateral and non-invasive tumor growth. Key Message: Through the summarized studies, we have been able to identify novel morphological and molecular features that could contribute to a better understanding of colorectal tumors and to improved clinical diagnosis.

show abstract

Section: Epigenetic Silencing Of Secreted Protein Acidic and Rich In mentioning

confidence: 65%

Section: Epigenetic Silencing Of Secreted Protein Acidic and Rich In mentioning

confidence: 77%

Section: Epigenetic Silencing Of Secreted Protein Acidic and Rich In mentioning

confidence: 92%

“…To identify DNA methylation associated with the TSA development, we analyzed a series of TSAs containing both protruding and flat components within the same tumors [15] (Fig. 3).…”

Section: Epigenetic Silencing Of Secreted Protein Acidic and Rich In mentioning

confidence: 99%

Section: Epigenetic Silencing Of Secreted Protein Acidic and Rich In mentioning

confidence: 99%

See 3 more Smart Citations

Integrated Analysis of the Endoscopic, Pathological and Molecular Characteristics of Colorectal Tumorigenesis

et al. 2018

Self Cite

View full text Add to dashboard Cite

show abstract

SMOC1 colocalizes with Alzheimer’s disease neuropathology and delays Aβ aggregation

Balcomb,

Johnston,

Kavanagh

et al. 2024

Acta Neuropathol

View full text Add to dashboard Cite

SMOC1 has emerged as one of the most significant and consistent new biomarkers of early Alzheimer’s disease (AD). Recent studies show that SMOC1 is one of the earliest changing proteins in AD, with levels in the cerebrospinal fluid increasing many years before symptom onset. Despite this clear association with disease, little is known about the role of SMOC1 in AD or its function in the brain. Therefore, the aim of this study was to examine the distribution of SMOC1 in human AD brain tissue and to determine if SMOC1 influenced amyloid beta (Aβ) aggregation. The distribution of SMOC1 in human brain tissue was assessed in 3 brain regions (temporal cortex, hippocampus, and frontal cortex) using immunohistochemistry in a cohort of 73 cases encompassing advanced AD, mild cognitive impairment (MCI), preclinical AD, and cognitively normal controls. The Aβ- and phosphorylated tau-interaction with SMOC1 was assessed in control, MCI, and advanced AD human brain tissue using co-immunoprecipitation, and the influence of SMOC1 on Aβ aggregation kinetics was assessed using Thioflavin-T assays and electron microscopy. SMOC1 strongly colocalized with a subpopulation of amyloid plaques in AD (43.8 ± 2.4%), MCI (32.8 ± 5.4%), and preclinical AD (28.3 ± 6.4%). SMOC1 levels in the brain strongly correlated with plaque load, irrespective of disease stage. SMOC1 also colocalized with a subpopulation of phosphorylated tau aggregates in AD (9.6 ± 2.6%). Co-immunoprecipitation studies showed that SMOC1 strongly interacted with Aβ in human MCI and AD brain tissue and with phosphorylated tau in human AD brain tissue. Thioflavin-T aggregation assays showed that SMOC1 significantly delayed Aβ aggregation in a dose-dependent manner, and electron microscopy confirmed that the Aβ fibrils generated in the presence of SMOC1 had an altered morphology. Overall, our results emphasize the importance of SMOC1 in the onset and progression of AD and suggest that SMOC1 may influence pathology development in AD.

show abstract

HOXA1, a breast cancer oncogene

Belpaire

Taminiau²,

Geerts³

et al. 2022

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

View full text Add to dashboard Cite

Epigenetic silencing ofSMOC1in traditional serrated adenoma and colorectal cancer

Cited by 26 publications

References 46 publications

Integrated Analysis of the Endoscopic, Pathological and Molecular Characteristics of Colorectal Tumorigenesis

Integrated Analysis of the Endoscopic, Pathological and Molecular Characteristics of Colorectal Tumorigenesis

SMOC1 colocalizes with Alzheimer’s disease neuropathology and delays Aβ aggregation

HOXA1, a breast cancer oncogene

Contact Info

Product

Resources

About