Prognostic and clinicopathological significance of TMEFF2, SMOC-2, and SOX17 expression in endometrial carcinoma

Alabiad, Mohamed Ali; Harb, Ola A.; Hefzi, Nabila; Ahmed, Rham Z.; Osman, Gamal; Shalaby, Abdalla; Alnemr, Amr Abd-Almohsen; Saraya, Yasser S.

doi:10.1016/j.yexmp.2021.104670

Cited by 16 publications

(13 citation statements)

References 50 publications

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“…Mutations in hSMOC2 have been found to be associated with defects in tooth development [49,50] and vitiligo [14,51,52]. Abnormal expression of SMOCs has also been associated with multiple cancers as well as kidney and pulmonary fibrosis [53][54][55][56][57][58][59].…”

Section: Discussionmentioning

confidence: 99%

C. elegansSMOC-1 interacts with both BMP and glypican to regulate BMP signaling

DeGroot

Williams

Chang

et al. 2023

Preprint

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Secreted modular calcium binding (SMOC) proteins are conserved matricellular proteins found in organisms from C. elegans to humans. SMOC homologs characteristically contain one or two extracellular calcium (EC) binding domain(s) and one or two thyroglobulin type-1 (TY) domain(s). SMOC proteins in Drosophila and Xenopus have been found to interact with cell surface heparan sulfate protein glycans (HSPGs) to exert both positive and negative influences on the conserved bone morphogenetic protein (BMP) signaling pathway. In this study, we used a combination of biochemical, structural modeling, and molecular genetic approaches to dissect the functions of the sole SMOC protein in C. elegans. We showed that SMOC-1 binds LON-2/glypican, as well as the mature domain of DBL-1/BMP. Moreover, SMOC-1 can simultaneously bind LON-2/glypican and DBL-1/BMP. The interaction between SMOC-1 and LON-2/glypican is mediated by the EC domain of SMOC-1, while the interaction between SMOC-1 and DBL-1/BMP involves full-length SMOC-1. We further showed that while SMOC-1(EC) is sufficient to promote BMP signaling when overexpressed, both the EC and TY domains are required for SMOC-1 function at the endogenous locus. Finally, when overexpressed, SMOC-1 can promote BMP signaling in the absence of LON-2/glypican. Taken together, our findings led to a model where SMOC-1 functions both negatively in a LON-2-dependent manner and positively in a LON-2-independent manner to regulate BMP signaling. Our work provides a mechanistic basis for how the evolutionarily conserved SMOC proteins regulate BMP signaling.

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Section: Discussionmentioning

confidence: 99%

C. elegansSMOC-1 interacts with both BMP and glypican to regulate BMP signaling

DeGroot

Williams

Chang

et al. 2023

Preprint

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“…SMOC2, which is a member of the SPARC family of matricellular proteins, is involved in the progression of multiple cancers. For instance, increased SMOC2 is associated with lymph node metastasis, distant metastasis, decreased chemosensitivity and a poor prognosis in endometrial cancer [ 8 , 17 ]. SMOC2 promotes proliferation and cell cycle progression in hepatocellular carcinoma cells [ 18 ].…”

Section: Discussionmentioning

confidence: 99%

“…Secreted modular calcium-binding protein 2 (SMOC2), which is a member of the secreted protein acidic and rich in cysteine (SPARC) family of matricellular proteins, interacts with matrix proteins, cell surface receptors, cytokines, proteasomes and other effector molecules to regulate cell-cell and cell-microenvironment communication [6]. In recent years, SMOC2 has been reported to be highly expressed in tumor tissues and to promote tumor migration, invasion and growth [7,8]. In addition to its role in tumor progression, it also regulates wound healing, bone growth, fibrosis and embryogenesis [9][10][11][12].…”

Section: Introductionmentioning

confidence: 99%

SMOC2 promotes aggressive behavior of fibroblast-like synoviocytes in rheumatoid arthritis through transcriptional and post-transcriptional regulating MYO1C

Liu

et al. 2022

Cell Death Dis

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Fibroblast-like synoviocytes (FLSs), play a key role in perpetuating synovial inflammation and bone erosion in rheumatoid arthritis (RA), however, the underlying mechanism(s) of RA FLSs activation and aggression remain unclear. Identifying endogenous proteins that selectively target FLSs is urgently needed. Here, we systematically identified that secreted modular calcium-binding protein 2 (SMOC2), was significantly increased in RA FLSs and synovial tissues. SMOC2 knockdown specifically regulated cytoskeleton remodeling and decreased the migration and invasion of RA FLSs. Mechanistically, cytoskeleton-related genes were significantly downregulated in RA FLSs with reduced SMOC2 expression, especially the motor protein myosin1c (MYO1C). SMOC2 controlled MYO1C expression by SRY-related high-mobility group box 4 (SOX4) and AlkB homolog 5 (ALKHB5) mediated-m6A modification through transcriptional and post-transcriptional regulation. Furthermore, intra-articular Ad-shRNA-SMOC2 treatment attenuated synovial inflammation as well as bone and cartilage erosion in rats with collagen-induced arthritis (CIA). Our findings suggest that increased SMOC2 expression in FLSs may contribute to synovial aggression and joint destruction in RA. SMOC2 may serve as a potential target against RA.

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“…Significant was defined as a Pvalue of less than 0.05. For all statistics, SPSS 22.0 for Windows (SPSS Inc., Chicago, IL, USA) and MedCalc windows (MedCalc Software bvba 13, Ostend, Belgium) were used (13) .…”

Section: Analyses Of Statistical Datamentioning

confidence: 99%

The Prognostic Value of Cancer Stem Cell Marker, Cluster of Differentiation 133 Expression in Stage III Colorectal Carcinoma

Alabiad

Said²,

Elhasadi³

et al. 2023

The Egyptian Journal of Hospital Medicine

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Background: Colorectal cancer (CRC) is the 3 rd most prevalent diagnosed cancer and the 4 th leading cause of cancer-related deaths globally. Nodal staging is significantly more essential in rectal cancer that detects most the therapy options.Objectives: This study aimed to evaluate CD133 expression in the colorectal carcinoma stage III using immunohistochemistry as well as its relationship to clinicopathological characteristics and patient outcomes. Patients and Methods:The study includes 60 cases with stage III CRC five years after surgical removal of the tumor and regular follow-up with the Departments of Medical and Clinical Oncology where clinicopathological and prognostic data are collected from the archives. The patients were classified into two groups, GI includes 22 CRC patients with relapse, and GII includes 38 CRC patients without relapse. Sixty archive paraffin blocks of primary resection and metastatic lymph nodes were extracted from the archives of the Pathology Department processed for CD133 immunohistochemistry. CD133 expression levels were assessed, analyzed, and correlated with clinicopathological and prognostic criteria. Results: Positive CD133 expression was significantly linked with old age ( P=0.034 ), large tumor size ( p < 0.001), perineural invasion (p = 0.0017), lympho-vascular invasion ( P < 0.001 ), high-grade ( p < 0.001 ), resistance to chemotherapy (p = 0.011), lymph nodes metastasis and relapse (p = 0.005*) and DFS (p = 0.005) Conclusion: CD133 expression in colorectal carcinoma is related to tumour progression and is considered a marker of poor prognosis and a strong indicator of relapse and poor survival. Moreover, CD133 stem cell marker may act as a targeted therapy in chemotherapeutic resistance patients with colorectal carcinoma.

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Prognostic and clinicopathological significance of TMEFF2, SMOC-2, and SOX17 expression in endometrial carcinoma

Cited by 16 publications

References 50 publications

C. elegansSMOC-1 interacts with both BMP and glypican to regulate BMP signaling

C. elegansSMOC-1 interacts with both BMP and glypican to regulate BMP signaling

SMOC2 promotes aggressive behavior of fibroblast-like synoviocytes in rheumatoid arthritis through transcriptional and post-transcriptional regulating MYO1C

The Prognostic Value of Cancer Stem Cell Marker, Cluster of Differentiation 133 Expression in Stage III Colorectal Carcinoma

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