PINCH-1 promotes Bcl-2-dependent survival signalling and inhibits JNK-mediated apoptosis in the primitive endoderm.

Montañez, Eloi; Karaköse, Esra; Tischner, Denise; Villunger, Andreas; Fässler, Reinhard

doi:10.1242/jcs.112029

Cited by 24 publications

(28 citation statements)

References 38 publications

(74 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover, activation of the phosphorylation of the Src family kinase and ERK1/2 is promoted by PINCH-1 (18). In the PrE, PINCH-1 is a pro-survival factor, which prevents apoptosis of PrE cells by modulating two independent signalling pathways; PINCH-1 inhibits JNK-mediated apoptosis by stabilizing the PINCH-1 binding protein RSU-1 and promotes Bcl-2-dependent pro-survival signalling downstream of integrins (13). In the present study, a correlation was identified between the activation of ERK signaling and the suppression of JNK signaling with the expression of PINCH in IAs.…”

Section: Discussionmentioning

confidence: 99%

“…Functional studies have revealed that PINCH loss-of-function leads to embryonic lethality and displays an abnormal epiblast polarity, impaired cavitation, detachment of primitive endoderm (PrE) and severe apoptosis of the PrE (11,12). PINCH-1 promotes B-cell lymphoma (Bcl)-2-dependent survival signalling and inhibits c-Jun N-terminal kinase (JNK)-mediated apoptosis in the PrE (13). Although the function of PINCH remains unknown, increasing numbers and accumulating evidence indicates that PINCH has been correlated with cancer development, invasion and metastasis in malignant cells, including breast cancer (14), pseudomyxoma peritonei (15), gastric adenocarcinoma (16) and rectal cancer (17).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Particularly interesting Cys-His-rich protein is highly expressed in human intracranial aneurysms and resists aneurysmal rupture

Peng

Shi

et al. 2016

Experimental and Therapeutic Medicine

View full text Add to dashboard Cite

Particularly interesting Cys-His-rich protein (PINCH) has several biological functions in cancer development, invasion and metastasis in malignant cells, and the expression of PINCH is upregulated in several cancer types, including breast cancer, gastric adenocarcinoma and rectal cancer. However, the contribution of PINCH to human cerebral aneurysms remains largely unknown. Therefore, the significance of PINCH expression in cerebral aneurysm growth and rupture was examined in the present study. The protein expression levels of alpha-smooth muscle actin, osteopontin (OPN), matrix metalloproteinase (MMP) 9 and PINCH were evaluated using immunohistochemistry and western blot analyses. The results demonstrate that the protein expression levels of OPN, MMP9 and PINCH in the unruptured intracranial aneurysm (UA) and ruptured intracranial aneurysm (RA) groups were markedly higher than those of the control group, whereas OPN and PINCH expression levels were decreased in the RA group compared to those of the UA group. In addition, there was a strong correlation between PINCH and tumor size (r=0.650 and P=0.0026), as well as between PINCH and OPN (r=0.639 and P=0.0033) in the unruptured cerebral aneurysms. However, the correlation between PINCH and tumor size (r=0.450 and P=0.1393) and between PINCH and OPN (r=0.366 and P=0.2426) revealed no obvious difference in the ruptured cerebral aneurysms. In conclusion, PINCH was highly expressed in the UAs, which may be a critical factor for preventing aneurysmal rupture. Moreover, PINCH may facilitate intracranial aneurysm progression, at least partially, through the activation of extracellular signal-regulated kinase signaling and the suppression of c-Jun N-terminal kinase signaling.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Particularly interesting Cys-His-rich protein is highly expressed in human intracranial aneurysms and resists aneurysmal rupture

Peng

Shi

et al. 2016

Experimental and Therapeutic Medicine

View full text Add to dashboard Cite

show abstract

“…The Ras suppressor protein 1 (Rsu1) is a leucine rich repeat protein that has a role in the IPP complex activity via binding to the LIM 5 domain of the adaptor protein PINCH1 (Kadrmas et al 2004; Dougherty et al 2005). Rsu1 co-localizes with PINCH1 at sites of focal adhesions in mammalian cells and muscle cell attachment in Drosophila (Kadrmas et al 2004; Dougherty et al 2005; Dougherty et al 2008; Montanez et al 2012). The inhibition of PINCH-ILK or PINCH-Rsu1 interaction results in decreased cell spreading and reduced motility of mammalian cells (Tu et al 1999; Zhang et al 2002a, b; Dougherty et al 2005) such that Rsu1 and PINCH1 are independently required for migration in the mammary epithelial cell line MCF10A (Simpson et al 2008).…”

Section: Introductionmentioning

confidence: 99%

“…Changes in the level of Rsu1 correlate with altered JNK activity (Masuelli and Cutler 1996; Kadrmas et al 2004; Dougherty et al 2005). Transient expression of Rsu1 in Cos1 cells inhibited growth factor-induced Jun kinase activity, and the ectopic expression of Rsu1 reduced JNK phosphorylation and apoptosis in PINCH1-deleted mouse primitive endoderm cells (Montanez et al 2012). Furthermore, Rsu1 is required for the viability of Drosophila embryos with disrupted PINCH-ILK binding (Elias et al 2012).…”

Section: Introductionmentioning

confidence: 99%

Rsu1 contributes to regulation of cell adhesion and spreading by PINCH1‐dependent and ‐ independent mechanisms

Gonzalez-Nieves

DeSantis

Cutler

2013

Journal of Cell Communication and Signaling

View full text Add to dashboard Cite

Cell adhesion and migration are complex processes that require integrin activation, the formation and dissolution of focal adhesion (FAs), and linkage of actin cytoskeleton to the FAs. The IPP (ILK, PINCH, Parvin) complex regulates FA formation via binding of the adaptor protein ILK to β1 integrin, PINCH and parvin. The signaling protein Rsu1 is linked to the complex via binding PINCH1. The role of Rsu1 and PINCH1 in adhesion and migration was examined in non-transformed mammary epithelial cells. Confocal microscopy revealed that the depletion of either Rsu1 or PINCH1 by siRNA in MCF10A cells decreased the number of focal adhesions and altered the distribution and localization of β1 integrin, vinculin, talin and paxillin without affecting the levels of FA protein expression. This correlated with reduced adhesion, failure to spread or migrate in response to EGF and a loss of actin stress fibers and caveolae. In addition, constitutive phosphorylation of actin regulatory proteins occurred in the absence of PINCH1. The depletion of Rsu1 caused significant reduction in PINCH1 implying that Rsu1 may function by regulating levels of PINCH1. However, while both Rsu1- or PINCH1-depleted cells retained the ability to activate adhesion signaling in response to EGF stimulation, only Rsu1 was required for EGF-induced p38 Map Kinase phosphorylation and ATF2 activation, suggesting an Rsu1 function independent from the IPP complex. Reconstitution of Rsu1-depleted cells with an Rsu1 mutant that does not bind to PINCH1 failed to restore FAs or migration but did promote spreading and constitutive p38 activation. These data show that Rsu1-PINCH1 association with ILK and the IPP complex is required for regulation of adhesion and migration but that Rsu1 has a critical role in linking integrin-induced adhesion to activation of p38 Map kinase signaling and cell spreading. Moreover, it suggests that Rsu1 may regulate p38 signaling from the IPP complex affecting other functions including survival.Electronic supplementary materialThe online version of this article (doi:10.1007/s12079-013-0207-5) contains supplementary material, which is available to authorized users.

show abstract

“…Studies showed that PINCH was involved in cell adhesion, migration, and apoptosis [13, 14]. PINCH protein can interact directly with integrin-linked kinase (ILK) and Nck-2 protein and is associated with integrin signaling and growth factor signaling pathway [15–18].…”

Section: Introductionmentioning

confidence: 99%

Overexpression of FXYD-3 Is Involved in the Tumorigenesis and Development of Esophageal Squamous Cell Carcinoma

et al. 2013

View full text Add to dashboard Cite

Objective. To investigate the association of FXYD-3 expression with clinicopathological variables and PINCH in patients with ESCC. Patients and Methods. Expression of FXYD-3 protein was immunohistochemically examined in normal esophageal mucous (n = 20) and ESCC (n = 64). Results. Expression of FXYD-3 in the cytoplasm markedly increased from normal esophageal epithelial cells to primary ESCC (P = 0.001). The expression of FXYD-3 was correlated with TNM stages and depth of tumor invasion. Furthermore, the cases with lymph node metastasis tended to show a higher frequency of positive expression than those without metastasis (P = 0.086), and FXYD-3 expression tended to be positively related to the expression of PINCH (P = 0.063). Moreover, the cases positive for both proteins had the highest frequency of lymph node metastasis (P = 0.001). However, FXYD-3 expression was not correlated with patient's gender (P = 0.847), age (P = 0.876), tumor location (P = 0.279), size (P = 0.771), grade of differentiation (P = 0.279), and survival (P = 0.113). Conclusion. Overexpression of FXYD-3 in the cytoplasm may play an important role in the tumorigenesis and development in the human ESCC, particularly in combination with PINCH expression.

show abstract

PINCH-1 promotes Bcl-2-dependent survival signalling and inhibits JNK-mediated apoptosis in the primitive endoderm.

Cited by 24 publications

References 38 publications

Particularly interesting Cys-His-rich protein is highly expressed in human intracranial aneurysms and resists aneurysmal rupture

Particularly interesting Cys-His-rich protein is highly expressed in human intracranial aneurysms and resists aneurysmal rupture

Rsu1 contributes to regulation of cell adhesion and spreading by PINCH1‐dependent and ‐ independent mechanisms

Overexpression of FXYD-3 Is Involved in the Tumorigenesis and Development of Esophageal Squamous Cell Carcinoma

Contact Info

Product

Resources

About