• 제목/요약/키워드: Focal adhesion

검색결과 92건 처리시간 0.029초

Targeting EGFL7 Expression through RNA Interference Suppresses Renal Cell Carcinoma Growth by Inhibiting Angiogenesis

  • Xu, Han-Feng;Chen, Lei;Liu, Xian-Dong;Zhan, Yun-Hong;Zhang, Hui-Hui;Li, Qing;Wu, Bin
    • Asian Pacific Journal of Cancer Prevention
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    • 제15권7호
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    • pp.3045-3050
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    • 2014
  • Renal cell carcinoma (RCC) is the most lethal of all urological cancers and tumor angiogenesis is closely related with its growth, invasion, and metastasis. Recent studies have suggested that epidermal growth factor-like domain multiple 7 (EGFL7) is overexpressed by many tumors, such as colorectal cancer and hepatocellular carcinoma; it is also correlated with progression, metastasis, and a poor prognosis. However, the role of EGFL7 in RCC is not clear. In this study, we examined how EGFL7 contributes to the growth of RCC using a co-culture system in vitro and a xenograft model in vivo. Downregulated EGFL7 expression in RCC cells affected the migration and tubule formation of HMEC-1 cells, but not their growth and apoptosis in vitro. The level of focal adhesion kinase (FAK) phosphorylation in HMEC-1 cells decreased significantly when co-cultured with 786-0/iEGFL7 cells compared with 786-0 cells. After adding rhEGFL7, the level of FAK phosphorylation in HMEC-1 cells was significantly elevated compared with phosphate-buffered saline (PBS) control. However, FAK phosphorylation was abrogated by EGFR inhibition. The average size of RCC local tumors in the 786-0/iEGFL7 group was noticeably smaller than those in the 786-0 cell group and their vascular density was also significantly decreased. These data suggest that EGFL7 has an important function in the growth of RCC by facilitating angiogenesis.

Identification and Functional Analysis of Differentially Expressed Genes Related to Metastatic Osteosarcoma

  • Niu, Feng;Zhao, Song;Xu, Chang-Yan;Chen, Lin;Ye, Long;Bi, Gui-Bin;Tian, Gang;Gong, Ping;Nie, Tian-Hong
    • Asian Pacific Journal of Cancer Prevention
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    • 제15권24호
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    • pp.10797-10801
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    • 2015
  • Background: To explore the molecular mechanisms of metastatic osteosarcoma (OS) by using the microarray expression profiles of metastatic and non-metastatic OS samples. Materials and Methods: The gene expression profile GSE37552 was downloaded from Gene Expression Omnibus database, including 2 human metastatic OS cell line models and 2 two non-metastatic OS cell line models. The differentially expressed genes (DEGs) were identified by Multtest package in R language. In addition, functional enrichment analysis of the DEGs was performed by WebGestalt, and the protein-protein interaction (PPI) networks were constructed by Hitpredict, then the signal pathways of the genes involved in the networks were performed by Kyoto Encyclopaedia of Genes and Genomes (KEGG) automatic annotation server (KAAS). Results: A total of 237 genes were classified as DEGs in metastatic OS. The most significant up- and down-regulated genes were A2M (alpha-2-macroglobulin) and BCAN (brevican). The DEGs were significantly related to the response to hormone stimulus, and the PPI network of A2M contained IL1B (interleukin), LRP1 (low-density lipoprotein receptor-related protein 1) and PDGF (platelet-derived growth factor). Furthermore, the MAPK signaling pathway and focal adhesion were significantly enriched. Conclusions: A2M and its interactive proteins, such as IL1B, LRP1 and PDGF may be candidate target molecules to monitor, diagnose and treat metastatic OS. The response to hormone stimulus, MAPK signaling pathway and focal adhesion may play important roles in metastatic OS.

Traction force microscopy for understanding cellular mechanotransduction

  • Hur, Sung Sik;Jeong, Ji Hoon;Ban, Myung Jin;Park, Jae Hong;Yoon, Jeong Kyo;Hwang, Yongsung
    • BMB Reports
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    • 제53권2호
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    • pp.74-81
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    • 2020
  • Under physiological and pathological conditions, mechanical forces generated from cells themselves or transmitted from extracellular matrix (ECM) through focal adhesions (FAs) and adherens junctions (AJs) are known to play a significant role in regulating various cell behaviors. Substantial progresses have been made in the field of mechanobiology towards novel methods to understand how cells are able to sense and adapt to these mechanical forces over the years. To address these issues, this review will discuss recent advancements of traction force microscopy (TFM), intracellular force microscopy (IFM), and monolayer stress microscopy (MSM) to measure multiple aspects of cellular forces exerted by cells at cell-ECM and cell-cell junctional intracellular interfaces. We will also highlight how these methods can elucidate the roles of mechanical forces at interfaces of cell-cell/cell-ECM in regulating various cellular functions.

레이저 소결 적층 시스템을 이용한 3차원 수산화인회석 인공지지체 제작에 관한 연구 (A Study on Fabrication of 3D Hydroxyapatite Scaffolds Using a Laser Sintering Deposition System)

  • 최승혁;사민우;김종영
    • 한국기계가공학회지
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    • 제21권4호
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    • pp.70-76
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    • 2022
  • Calcium-phosphate-based bioceramics are promising biomaterials for scaffolds because they can assist in bone regeneration. In this study, a laser sintering deposition system was developed, and 3D hydroxyapatite (HA) scaffolds were fabricated. The main process conditions of the HA scaffolds were laser power, table velocity, and laser focal distance. As the laser power increased, the line width, line height, and layer thickness also increased. Further, the line width, line height, and layer thickness decreased as the table velocity increased. As the laser focal distance increased, the line width increased, but the line height and layer thickness decreased. The fabricated green scaffolds were sintered at 1050 ℃ and 1150 ℃. The sintered scaffolds had a uniform and continuous interconnected shape, with pore sizes ranging from 850 to 950 ㎛ having 53% porosity. The compressive strength of the scaffolds decreased from 0.72 MPa (1050 ℃) to 0.53 MPa (1150 ℃). The biocompatibility of the scaffolds was investigated by analyzing the adhesion of osteoblast-like MG-63 cells cultured on the surfaces of the scaffolds. The results indicate that the scaffold sintered at 1050 ℃ had good mechanical and biological properties compared to that at 1150 ℃.

상아모세포의 I 형 아교질에 대한 부착 (THE ADHESION OF ODONTOBLAST TO TYPE I COLLAGEN)

  • 안명기;정태성;김신
    • 대한소아치과학회지
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    • 제37권3호
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    • pp.308-316
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    • 2010
  • 상아모세포는 부착분자들을 이용하여 기질에 부착하는 세포이며, 인테그린과 같은 부착분자들이 일련의 세포와 세포외기질을 인지하는 신호전달분자로 알려져 있다. 본 연구의 목적은 상아모세포(MDPC-23 세포)와 I형 아교질과의 상호작용과 TGF-${\beta}1$과 TNF-${\alpha}$가 세포부착분자의 발현에 미치는 영향을 알아보기 위해 시행하였다. 본 연구에서 MDPC-23 세포는 농도의존적으로 I형 아교질에 부착했으며, 면역형광염색법에서 MDPC-23 세포가 아교질에 부착할 때, 국소부착점에서 인테그린 ${\alpha}1$, ${\alpha}2$, CD44, FAK 그리고 paxillin의 발현양상을 관찰할 수 있었다. 싸이토카인 TGF-${\beta}1$은 MDPC-23 세포의 아교질에 대한 부착성 및 인테그린 ${\alpha}1$, ${\alpha}2$와 chondroitin sulfate의 발현을 증가시켰으며, RT-PCR의 결과에서는 인테그린 ${\alpha}1$의 mRNA의 양이 TGF-${\beta}1$에 의해서 증가되었음을 확인하였다. 결론적으로 MDPC-23 세포는 아교질에 부착 친화성을 갖고 있으며, 부착 시에 인테그린 ${\alpha}1$, ${\alpha}2$와 CD44 그리고 chondroitin sulfate와 같은 부착분자들이 관여한다. 그리고 TGF-${\beta}1$은 인테그린 ${\alpha}1$, ${\alpha}2$ 그리고 chondroitin sulfate와 같은 부착분자의 발현을 증가시켰다.

Increased α2-6 sialylation of endometrial cells contributes to the development of endometriosis

  • Choi, Hee-Jin;Chung, Tae-Wook;Choi, Hee-Jung;Han, Jung Ho;Choi, Jung-Hye;Kim, Cheorl-Ho;Ha, Ki-Tae
    • Experimental and Molecular Medicine
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    • 제50권12호
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    • pp.9.1-9.12
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    • 2018
  • Endometriosis is a disease characterized by implants of endometrial tissue outside the uterine cavity and is strongly associated with infertility. Focal adhesion of endometrial tissue to the peritoneum is an indication of incipient endometriosis. In this study, we examined the effect of various cytokines that are known to be involved in the pathology of endometriosis on endometrial cell adhesion. Among the investigated cytokines, transforming growth factor-${\beta}1$ ($TGF-{\beta}1$) increased adhesion of endometrial cells to the mesothelium through induction of ${\alpha}2-6$ sialylation. The expression levels of ${\beta}$-galactoside ${\alpha}2-6$ sialyltransferase (ST6Gal) 1 and ST6Gal2 were increased through activation of $TGF-{\beta}RI/SMAD2/3$ signaling in endometrial cells. In addition, we discovered that terminal sialic acid glycan epitopes of endometrial cells engage with sialic acid-binding immunoglobulin-like lectin-9 expressed on mesothelial cell surfaces. Interestingly, in an in vivo mouse endometriosis model, inhibition of endogenous sialic acid binding by a $NeuAc{\alpha}2-6Gal{\beta}1$-4GlcNAc injection diminished $TGF-{\beta}1$-induced formation of endometriosis lesions. Based on these results, we suggest that increased sialylation of endometrial cells by $TGF-{\beta}1$ promotes the attachment of endometrium to the peritoneum, encouraging endometriosis outbreaks.

Homozygous Missense Epithelial Cell Adhesion Molecule Variant in a Patient with Congenital Tufting Enteropathy and Literature Review

  • Guvenoglu, Merve;Simsek-Kiper, Pelin Ozlem;Kosukcu, Can;Taskiran, Ekim Z.;Saltik-Temizel, Inci Nur;Gucer, Safak;Utine, Eda;Boduroglu, Koray
    • Pediatric Gastroenterology, Hepatology & Nutrition
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    • 제25권6호
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    • pp.441-452
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    • 2022
  • Congenital diarrheal disorders (CDDs) with genetic etiology are uncommon hereditary intestinal diseases characterized by chronic, life-threatening, intractable watery diarrhea that starts in infancy. CDDs can be mechanistically divided into osmotic and secretory diarrhea. Congenital tufting enteropathy (CTE), also known as intestinal epithelial dysplasia, is a type of secretory CDD. CTE is a rare autosomal recessive enteropathy that presents with intractable neonatal-onset diarrhea, intestinal failure, severe malnutrition, and parenteral nutrition dependence. Villous atrophy of the intestinal epithelium, crypt hyperplasia, and irregularity of surface enterocytes are the specific pathological findings of CTE. The small intestine and occasionally the colonic mucosa include focal epithelial tufts. In 2008, Sivagnanam et al. discovered that mutations in the epithelial cell adhesion molecule (EpCAM, MIM# 185535) were the genetic cause of CTE (MIM# 613217). More than a hundred mutations have been reported to date. Furthermore, mutations in the serine peptidase inhibitor Kunitz type 2 (SPINT2, MIM# 605124) have been linked to syndromic CTE. In this study, we report the case of a 17-month-old male infant with congenital diarrhea. Despite extensive etiological workup, no etiology could be established before admission to our center. The patient died 15 hours after being admitted to our center in a metabolically decompensated state, probably due to a delay in admission and diagnosis. Molecular autopsy with exome sequencing revealed a previously reported homozygous missense variant, c.757G>A, in EpCAM, which was confirmed by histopathological examination.

혈관내피성장인자에 관한 고찰 (Review of Vascular Endothelial Growth Factor)

  • 김석범;김동현;송주영;김진상
    • The Journal of Korean Physical Therapy
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    • 제14권1호
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    • pp.219-226
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    • 2002
  • Vascular endothelial growth factors(VEGFs) constitute a group of structurally and functionally related growth factor that modulate many important physiological functions of endothelial cells, especially angiogenesis. This paper explain substance, which participate in signaling transduction of VEGF, including Bcl-2, caspase, focal adhesion kinase(FAK), integrin ${\alpha}v{\beta}3$, MAP kinase, nitric oxide(NO)and prostacyclin(PGI2). Physical therapy enhance angiogenesis for repairment of injury which as wound healing, muscle contusion, cerebrovascular disease, rheumatoid arthritis. Therefore this review assist understanding for mechanism of physical therapy as therapeutic angiogenesis.

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TM4SF5-mediated protein-protein networks and tumorigenic roles

  • Lee, Jung Weon
    • BMB Reports
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    • 제47권9호
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    • pp.483-487
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    • 2014
  • Transmembrane 4 L six family member 5 (TM4SF5), as a membrane glycoprotein with 4 transmembrane domains, is similar to the tetraspanins in terms of membrane topology and plays important roles in tumorigenesis and tumor metastasis. Especially, TM4SF5 appears to form a massive protein-protein complex consisting of diverse membrane proteins and/or receptors in addition to cytosolic signaling molecules to regulate their signaling activities during the pathological processes. TM4SF5 is shown to interact with integrins ${\alpha}2$, ${\alpha}5$, and ${\beta}1$, EGFR, IL6R, CD151, focal adhesion kinase (FAK), and c-Src. This review focuses on the significance of the interactions with regards to TM4SF5-positive tumorigenesis and metastasis.