Signaling adaptor protein Crk is indispensable for malignant feature of glioblastoma cell line KMG4

Wang, Lei; Tabu, Kouichi; Kimura, Taichi; Tsuda, Masumi; Linghu, Hua; Tanino, Mishie; Kaneko, Sadao; Nishihara, Hiroshi; Tanaka, Shinya

doi:10.1016/j.bbrc.2007.08.106

Cited by 39 publications

(49 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…CrkI is a more potent transforming gene than CrkII and CrkL in part because, like v-Crk, it lacks a C-terminal regulatory phosphorylation site (3). Overexpression of Crk and CrkL has been reported in several human cancers, including oral squamous cell carcinoma (5), ovarian carcinoma (6), colon cancer (7), lung cancer (8, 9), breast cancer (10, 11), gastric cancer (12), and glioblastoma (13,14). Reduced expression of either Crk or CrkL by RNA interference-mediated knockdown lowered the in vivo tumor formation of human ovarian (15), synovial sarcoma (16), glioblastoma (14), breast cancer (10), head and neck squamous cell carcinoma (17), and rhabdomyosarcoma (18) cell lines.…”

Section: Edited By Xiao-fan Wangmentioning

confidence: 99%

“…Overexpression of Crk and CrkL has been reported in several human cancers, including oral squamous cell carcinoma (5), ovarian carcinoma (6), colon cancer (7), lung cancer (8,9), breast cancer (10,11), gastric cancer (12), and glioblastoma (13,14). Reduced expression of either Crk or CrkL by RNA interference-mediated knockdown lowered the in vivo tumor formation of human ovarian (15), synovial sarcoma (16), glioblastoma (14), breast cancer (10), head and neck squamous cell carcinoma (17), and rhabdomyosarcoma (18) cell lines. Taken together, these reports imply that elevated levels of Crk family proteins promote cell transformation and enhance tumor cell growth (for review see Refs.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Fibroblast Growth Requires CT10 Regulator of Kinase (Crk) and Crk-like (CrkL)

Park

Koptyra

Curran

2016

Journal of Biological Chemistry

View full text Add to dashboard Cite

Edited by Xiao-Fan WangThe chicken tumor virus oncoprotein, v-Crk, induces a substantial increase in protein tyrosine phosphorylation through protein-protein interactions mediated by its SH2 2 and SH3 domains, leading to cell transformation (1). CrkII and Crk-like (CrkL) represent closely related cellular homologues of v-Crk and have similar structures and functions (2). CrkI is a splice variant of CrkII that lacks the C-terminal SH3 domain. Crk family proteins (CrkI, CrkII, and CrkL) interact with many proteins through their SH2 and SH3 domains. Overexpression of Crk family proteins induces transformation of cultured cells (3,4). CrkI is a more potent transforming gene than CrkII and CrkL in part because, like v-Crk, it lacks a C-terminal regulatory phosphorylation site (3). Overexpression of Crk and CrkL has been reported in several human cancers, including oral squamous cell carcinoma (5), ovarian carcinoma (6), colon cancer (7), lung cancer (8, 9), breast cancer (10, 11), gastric cancer (12), and glioblastoma (13,14). Reduced expression of either Crk or CrkL by RNA interference-mediated knockdown lowered the in vivo tumor formation of human ovarian (15), synovial sarcoma (16), glioblastoma (14), breast cancer (10), head and neck squamous cell carcinoma (17), and rhabdomyosarcoma (18) cell lines. Taken together, these reports imply that elevated levels of Crk family proteins promote cell transformation and enhance tumor cell growth (for review see Refs. 19 and 20).To investigate functions of endogenous Crk and CrkL in biological processes at the cellular level, we developed mouse strains and cell lines harboring individual and combined floxed alleles of Crk and CrkL. Application of the Cre-loxP recombination-based conditional knock-out approach to cultured fibroblasts enabled us to demonstrate that endogenous Crk and CrkL are important for maintaining cell structural integrity and proper cell motility (21). We also discovered that Crk and CrkL are required for cell transformation induced by viral oncogenes (22). Here we utilized the conditional knock-out system to examine whether endogenous Crk and CrkL are required for cell growth. Our findings clearly demonstrate that Crk and CrkL play essential, overlapping roles in fibroblast proliferation by enabling cells to progress from the G 1 phase to the S phase. Our study also demonstrates that expression of any one protein among CrkI, CrkII, and CrkL at physiological levels is sufficient to secure cell proliferation. ResultsCrk and CrkL Are Essential for Fibroblast Proliferation-We used the Neon system (Life Technologies) to achieve rapid and efficient gene expression in growing fibroblasts by transduction of synthetic mRNA (synRNA). To reduce innate immune responses and increase ectopic protein expression, we synthesized mRNA using the modified ribonucleotides, pseudo-UTP, and methyl-CTP (23,24). When fibroblasts immortalized by T antigen or the 3T3 protocol were transfected with synthetic green fluorescent protein mRNA (synGFP), both cell types in monolayer cul...

show abstract

Section: Edited By Xiao-fan Wangmentioning

confidence: 99%

mentioning

confidence: 99%

Fibroblast Growth Requires CT10 Regulator of Kinase (Crk) and Crk-like (CrkL)

Park

Koptyra

Curran

2016

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…The CRK family has been shown to be overexpressed in lung adenocarcinoma 24 , human colon cancers 25 and malignant glioblastoma 26,27 . High levels of CRK mRNA and protein expression correlate with increased tumour aggressiveness in lung, contributing to poor prognosis and shorter survival 24 .…”

Section: Integrin Adaptors In Cancermentioning

confidence: 99%

“…CRK silencing remarkably suppresses tumour formation in human synovial sarcoma cell xenografts and invasive growth in vivo 91,92 . In glioblastoma cells, CRK over-expression increases cell migration and invasion, likely through an association with DOCK180 26 and its silencing suppresses early attachment to laminin, cell motility and growth 27 . Recent studies show that CRK is down-regulated by miR-126 microRNA in lung cancer cells resulting in impaired cell adhesion, migration and invasion 93 …”

Section: Migration and Invasionmentioning

confidence: 99%

Integrin signalling adaptors: not only figurants in the cancer story

et al. 2010

View full text Add to dashboard Cite

Current evidence highlights the ability of adaptor (or scaffold) proteins to create signalling platforms that drive cellular transformation upon integrin-dependent adhesion and growth factor receptor activation. The understanding of the biological effects regulated by these adaptors in tumours might be crucial for the identification of novel targets and the development of innovative therapeutic strategies for human cancer. In this review we will discuss the relevance of adaptor proteins in signalling originating from integrin-mediated cell-extracellular matrix (ECM) adhesion and growth factor stimulation within the context of cell transformation and tumour progression.Herein, we will specifically underline the contribution of p130CAS, NEDD9, CRK, and the IPP complex (ILK, PINCH and PARVIN) to cancer, along with the more recently identified p140CAP.

show abstract

“…KMG4 cell line was kindly provided by Dr. Kazuo Tabuchi (Saga University, Saga, Japan; ref. 30). LN382, LN308, and LN235 cell lines were kindly provided by Dr. Erwin G. Van Meir (Emory University School of Medicine, Atlanta, GA; refs.…”

Section: Cellsmentioning

confidence: 99%

STAT3 Inhibition Overcomes Temozolomide Resistance in Glioblastoma by Downregulating MGMT Expression

Wang

Yachi

Mahabir

et al. 2012

Molecular Cancer Therapeutics

Self Cite

167

139

View full text Add to dashboard Cite

Glioblastoma multiforme (GBM) is one of the most aggressive human tumors with a poor prognosis. Current standard treatment includes chemotherapy with the DNA-alkylating agent temozolomide concomitant with surgical resection and/or irradiation. However, a number of cases are resistant to temozolomide-induced DNA damage due to elevated expression of the DNA repair enzyme O 6 -methylguanine-DNA methyltransferase (MGMT). Here, we show that upregulation of both MGMT and STAT3 was accompanied with acquisition of temozolomide resistance in the GBM cell line U87. Inactivation of STAT3 by inhibitor or short hairpin RNA (shRNA) downregulated MGMT expression in GBM cell lines. MGMT upregulation was not observed by the treatment of interleukin (IL)-6 which is a strong activator of STAT3. Contrarily, forced expressed MGMT could be downregulated by STAT3 inhibitor which was partially rescued by the proteasome inhibitor, MG132, suggesting the STAT3-mediated posttranscriptional regulation of the protein levels of MGMT. Immunohistochemical analysis of 44 malignant glioma specimens showed significant positive correlation between expression levels of MGMT and phosphorylated STAT3 (p-STAT3; P < 0.001, r ¼ 0.58). Importantly, the levels of both MGMT and p-STAT3 were increased in the recurrence compared with the primary lesion in paired identical tumors of 12 cases. Finally, we showed that STAT3 inhibitor or STAT3 knockdown potentiated temozolomide efficacy in temozolomide-resistant GBM cell lines. Therefore, STAT3 inhibitor might be one of the candidate reagents for combination therapy with temozolomide for patients with temozolomide-resistant GBM.

show abstract

Signaling adaptor protein Crk is indispensable for malignant feature of glioblastoma cell line KMG4

Abstract: These results suggest that Crk is required for early attachment to laminin, cell motility, and growth of glioblastoma cell line KMG4.3

Cited by 39 publications

References 38 publications

Fibroblast Growth Requires CT10 Regulator of Kinase (Crk) and Crk-like (CrkL)

Fibroblast Growth Requires CT10 Regulator of Kinase (Crk) and Crk-like (CrkL)

Integrin signalling adaptors: not only figurants in the cancer story

STAT3 Inhibition Overcomes Temozolomide Resistance in Glioblastoma by Downregulating MGMT Expression

Contact Info

Product

Resources

About