TGF‐β1 enhances βig‐h3‐mediated keratinocyte cell migration through the α3β1 integrin and PI3K

Jeong, Ha Won; Kim, In San

doi:10.1002/jcb.20110

Cited by 58 publications

(59 citation statements)

References 34 publications

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“…Low levels of activated Akt are observed in human RCC cells (20). Some important factors, including EGF, VEGF, and TGF-b, are involved in the tumorigenesis of human carcinoma through activation of PI3K/Akt signaling cascade (38)(39)(40). These growth factors derived from RCC may be responsible for the constitutive activation of Akt.…”

Section: Discussionmentioning

confidence: 99%

TNF-α Induces Epithelial–Mesenchymal Transition of Renal Cell Carcinoma Cells via a GSK3β-Dependent Mechanism

Tang

Chuang

et al. 2012

Molecular Cancer Research

107

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TNF-a is a cytokine with antitumorigenic property. In contrast, low dose, chronic TNF-a production by tumor cells or stromal cells may promote tumor growth and metastasis. Serum levels of TNF-a are significantly elevated in renal cell carcinoma (RCC) patients. Here, we showed that TNF-a induced epithelial-mesenchymal transition (EMT) and promoted tumorigenicity of RCC by repressing E-cadherin, upregulating vimentin, activating MMP9, and invasion activities. In addition, TNF-a treatment inhibited glycogen synthase kinase 3b (GSK-3b) activity through serine-9 phosphorylation mediated by the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) pathway in RCC cells. Inhibition of PI3K/AKT by LY294002 reactivated GSK-3b and suppressed the TNFa-induced EMT of RCC cells. Inactivation of GSK-3b by LiCl significantly increased MMP9 activity and EMT of RCC cells. Activation of GSK-3b by transduction of constitutively active GSK-3b into RCC cells suppressed TNFa-mediated anchorage-independent growth in soft agar and tumorigenicity in nude mice. Overexpression of a kinase-deficient GSK-3b, in contrast, potentiated EMT, anchorage-independent growth and drastically enhanced tumorigenicity in vivo. Most importantly, a 15-fold inactivation of GSK-3b activity, 3-fold decrease of E-cadherin, and 2-fold increase of vimentin were observed in human RCC tumor tissues. These results indicated that inactivation of GSK-3b plays a pivotal role in the TNF-a-mediated tumorigenesis of RCC. Mol Cancer Res; 10(8); 1109-19. Ó2012 AACR. IntroductionRenal cell carcinoma (RCC) is the tenth most common cause of cancer-related deaths worldwide (1). Although surgery is often curative, 30% of patients will present with metastases at the time of initial diagnosis (1). The 5-year survival rate is only 5% in metastatic RCC as advanced RCC is resistant to chemotherapy and radiotherapy (2, 3). Previous studies indicated immunotherapy is relatively effective against RCC (2, 3). However, the response rate is only 15% to 20% (1-3). Therefore, defining the factors involved in disease progression and metastasis will provide novel molecular targets for the development of effective therapies.

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Section: Discussionmentioning

confidence: 99%

TNF-α Induces Epithelial–Mesenchymal Transition of Renal Cell Carcinoma Cells via a GSK3β-Dependent Mechanism

Tang

Chuang

et al. 2012

Molecular Cancer Research

107

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“…For example, TGF-␤ stimulation of FAK 397 enhances migration in keratinocytes and hepatocarcinoma cells. 74,75 TGF-␤-induced fibroblast differentiation to myoblasts was shown to require adhesiondependent FAK activation by some investigators, 73 although others have suggested that in some cases FAK effects on differentiation may be mediated by interactions with another growth factor. 76 Finally, TGF-␤ acts synergistically with integrins to activate FAK and induce phenotypic changes in rat podocytes.…”

Section: Discussionmentioning

confidence: 99%

Transforming Growth Factor-β Stimulates Intestinal Epithelial Focal Adhesion Kinase Synthesis via Smad- and p38-Dependent Mechanisms

Walsh

Ampasala

Hatfield

et al. 2008

The American Journal of Pathology

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Focal adhesion kinase (FAK) regulates cell migration, proliferation, and apoptosis. FAK protein is reduced at the edge of migrating gut epithelial sheets in vitro, but it has not been characterized in restitutive gut mucosa in vivo. Here we show that FAK and activated phospho-FAK (FAK 397 ) immunoreactivity was lower in epithelial cells immediately adjacent to human gastric and colonic ulcers in vivo, but dramatically increased in epithelia near the ulcers, possibly reflecting stimulation by growth factors absent in vitro. Transforming growth factor (TGF)-␤, but not fibroblast growth factor, platelet-derived growth factor, or vascular endothelial growth factor, increased FAK levels in Caco-2 and IEC-6 cells. Epithelial immunoreactivity to TGF-␤ and phospho-Smad3 was also higher near the ulcers, varying in parallel with FAK. The TGF-␤ receptor antagonist SB431542 completely blocked TGF-␤-induced Smad2/3 and p38 activation in IEC-6 cells. SB431542 , the p38 antagonist SB203580 , and siRNA-mediated reduction of Smad2 and p38␣ prevented TGF-␤ stimulation of both FAK transcription and translation (as measured via a FAK promoter-luciferase construct). Survival and function of epithelial cells depends critically on interactions between the extracellular matrix and cell surface integrins. These interactions are mediated through focal adhesions, multicomponent juxtamembrane structures that lie at the convergence of integrin adhesion, signaling, and the cytoskeleton.1 Focal adhesion kinase (FAK) is an important nonreceptor tyrosine kinase within the focal adhesion complex.2 Originally described as being rapidly tyrosine phosphorylated on integrin-mediated cell-matrix adhesion, FAK is now known to be activated during epithelial cell motility and phosphorylated at both serine and tyrosine residues by various factors.3-5 Once localized to sites of transmembrane integrin receptor clustering, tyrosine-phosphorylated FAK plays a central role in signal transduction triggered by diverse extracellular signals 6 and represents a convergent point for synergistic interaction between signal pathways activated by growth factors and integrins.7 FAK binds to different signaling proteins via Src homology 2 (SH2) and SH3 recognition sites, acting as a scaffold and transmitting signals crucial to cell survival, motility, proliferation, and differentiation.8 FAK also regulates the cycle of focal contact formation and disassembly required for efficient cell movement and thus, mucosal restitution. 9Levels of FAK protein expression and/or activation have been correlated to phenotypic changes that affect cell differentiation and function, notably adhesion and migration, in a number of tissues. 10 -13 Targeted FAK deletion in vascular endothelial cells leads to apoptosis and aberrant cell movement whereas FAK overexpression results in increased angiogenesis.14,15 Total and activated FAK levels are also directly related to the state of differentiation in human colon cancer. 16 Induction of differentiation in dedifferentiated, rounded, detached Co...

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“…TGFBI protein contains a signal peptide in the first 24 amino acid residues at the N-terminus, a cysteine-rich EMI domain, four highly conserved fasciclin (FAS) domains and several integrin-binding motifs including the RGD motif in the C-terminus, which serves as a ligand-recognition site for several integrins (LeBaron et al 1995, Ohno et al 1999, Bae et al 2002, Jeong & Kim 2004, Kim & Kim 2008. Other integrin-binding motifs include the NKDIL motif (amino acids 354-358) (Kim et al 2000), the EPDIM motif (amino acids 617-621) (Kim et al 2000) in the second and fourth FAS-1 domains, respectively, and the YH18 motif (amino acids 563-580) in the fourth FAS-1 domain, which can support αvβ5 integrin-mediated adhesion of lung fibroblast MRC-5 cells , vascular smooth muscle cells (Lee et al 2006) and endothelial cells (Nam et al 2003).…”

Section: Role Of Tgfbi In Ovarian Cancermentioning

confidence: 99%

“…Effects of TGFBI on adhesion are mediated through interactions with various integrins including α1β1, α3β1, αvβ3 and αvβ5 (LeBaron et al 1995, Ohno et al 1999, Bae et al 2002, Jeong & Kim 2004, Kim & Kim 2008) via the different integrin-binding motifs. TGFBI also functions as a linker protein and connects many matrix proteins including collagens (type I, II and IV), fibronectin (Billings et al 2002) and proteoglycans (biglycan and decorin) with each other (Gibson et al 1997, Billings et al 2002, Hanssen et al 2003, Reinboth et al 2006.…”

Section: Role Of Tgfbi In Ovarian Cancermentioning

confidence: 99%

WOMEN IN CANCER THEMATIC REVIEW: Ovarian cancer–peritoneal cell interactions promote extracellular matrix processing

Ricciardelli

Lokman

Ween

et al. 2016

Endocrine-Related Cancer

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Ovarian cancer has a distinct tendency for metastasising via shedding of cancerous cells into the peritoneal cavity and implanting onto the peritoneum that lines the pelvic organs. Once ovarian cancer cells adhere to the peritoneal cells, they migrate through the peritoneal layer and invade the local organs. Alterations in the extracellular environment are critical for tumour initiation, progression and intra-peritoneal dissemination. To increase our understanding of the molecular mechanisms involved in ovarian cancer metastasis and to identify novel therapeutic targets, we recently studied the interaction of ovarian cancer and peritoneal cells using a proteomic approach. We identified several extracellular matrix (ECM) proteins including, fibronectin, TGFBI, periostin, annexin A2 and PAI-1 that were processed as a result of the ovarian cancerperitoneal cell interaction. This review focuses on the functional role of these proteins in ovarian cancer metastasis. Our findings together with published literature support the notion that ECM processing via the plasminogen-plasmin pathway promotes the colonisation and attachment of ovarian cancer cells to the peritoneum and actively contributes to the early steps of ovarian cancer metastasis.

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TGF‐β1 enhances βig‐h3‐mediated keratinocyte cell migration through the α3β1 integrin and PI3K

Cited by 58 publications

References 34 publications

TNF-α Induces Epithelial–Mesenchymal Transition of Renal Cell Carcinoma Cells via a GSK3β-Dependent Mechanism

TNF-α Induces Epithelial–Mesenchymal Transition of Renal Cell Carcinoma Cells via a GSK3β-Dependent Mechanism

Transforming Growth Factor-β Stimulates Intestinal Epithelial Focal Adhesion Kinase Synthesis via Smad- and p38-Dependent Mechanisms

WOMEN IN CANCER THEMATIC REVIEW: Ovarian cancer–peritoneal cell interactions promote extracellular matrix processing

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