Crk at the Quarter Century Mark: Perspectives in Signaling and Cancer

Kumar, Sushil; Fajardo, J. Eduardo; Birge, Raymond B.; Sriram, Ganapathy

doi:10.1002/jcb.24749

Cited by 31 publications

(28 citation statements)

References 44 publications

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“…CRK is involved in signal transduction through protein-protein interactions. CRK mediates signal propagation of multiple cancer-related processes, such as cell proliferation and migration [18]. In several malignancies for instance lung cancer, CRK was found to be overexpressed [26].…”

Section: Discussionmentioning

confidence: 99%

New miRNA expression abnormalities in laryngeal squamous cell carcinoma

Cybula

Wieteska

Józefowicz-Korczyńska

et al. 2016

CBM

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Abstract. BACKGROUND:Although the development of novel diagnostic and treatment strategies concerning laryngeal cancer is highly intensive, the survival rate remains virtually unchanged. Small non-coding RNAs appear to be very promising biomarkers -and so remain the focus of extensive investigation in laryngeal cancer. OBJECTIVE: We examined the expression of five miRNA and five genes related to cancer whether they could be potential laryngeal cancer biomarkers. METHODS:We performed an analysis in 47 patients diagnosed with laryngeal cancer. The qPCR technique was used to investigate the expression profile. RESULTS: While miR-21-3p and miR-525-5p were found to be significantly up-regulated, miR-139-3p and miR-885-5p expression is lower in laryngeal cancer. Moreover, PIK3R1 and HACE1 were found to be also down-regulated. CONCLUSIONS: The change in miRNA expression is frequent than the expression of other tested genes. The expression of passenger strands such as miR-21-3p and miR-139-3p, which are rarely investigated, is also significantly affected in laryngeal cancer. While PIK3R1, HACE1, miR-139-3p, and miR-885-5p may act as tumor suppressor genes in the studied tumour type, miR-21-3p and miR-525-5p seem to have oncogenic properties. Our findings suggest that miR-885-5p and PIK3R1 are the best indicators for the classification of laryngeal cancer tissue and normal mucosa.

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Section: Discussionmentioning

confidence: 99%

New miRNA expression abnormalities in laryngeal squamous cell carcinoma

Cybula

Wieteska

Józefowicz-Korczyńska

et al. 2016

CBM

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“…CrkL is best known as a key substrate and effective downstream molecule of the BCR-ABL1 oncogenic tyrosine kinase in breast cancer [7] and bladder cancer [8]. CrkL contains the domain structure SH2-SH3-SH3 and has been reported to bind through its N-terminal SH3 domain with various signaling molecules such as Sos1 and C3G [9], two guanine nucleotide exchange factors for the Ras family of small GTPbinding proteins.…”

Section: Introductionmentioning

confidence: 99%

Crk-like adapter protein regulates CCL19/CCR7-mediated epithelial-to-mesenchymal transition via ERK signaling pathway in epithelial ovarian carcinomas

et al. 2015

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Recent studies have suggested that Crk-like adapter protein (CrkL) and epithelial-to-mesenchymal transition (EMT) induced by CCL19/CCR7 play an important role in ovarian epithelial carcinogenesis. However, the regulatory mechanisms of CrkL on the CCL19/CCR7 signaling pathways in epithelial ovarian carcinomas (EOC) are not well characterized. Here, CCR7 and CrkL proteins were tested in 30 EOC tissues and cell lines. In vitro, the roles of CrkL in CCL19-stimulated SKOV-3 cell invasion and migration were investigated. In this work, CCR7 and CrkL over-expressed in EOC tissues and cell lines and correlated with FIGO stage and lymph node metastasis. Moreover, CCR7 and CrkL serve as an independent prognostic factor. In SKOV-3 cells, CrkL knockdown markedly suppressed the CCL19-stimulated expression of p-ERK and EMT biomarkers (N-cadherin, Snail and MMP9), compared with control. In contrast, p-AKT expression level did not change. On the other hand, functional analysis revealed CrkL knockdown could significantly decrease SKOV-3 cell invasion number of transwell invasion assay, and wound closure area of wound healing assay, compared to control. In conclusion, CrkL regulates CCL19/CCR7-induced EMT via ERK signaling pathway in EOC patients, which further suggested CrkL could be suggested as an efficient target in ovarian cancer treatment.

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“…The 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).…”

mentioning

confidence: 99%

“…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.…”

mentioning

confidence: 99%

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

Park

Koptyra

Curran

2016

Journal of Biological Chemistry

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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...

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Crk at the Quarter Century Mark: Perspectives in Signaling and Cancer

Cited by 31 publications

References 44 publications

New miRNA expression abnormalities in laryngeal squamous cell carcinoma

New miRNA expression abnormalities in laryngeal squamous cell carcinoma

Crk-like adapter protein regulates CCL19/CCR7-mediated epithelial-to-mesenchymal transition via ERK signaling pathway in epithelial ovarian carcinomas

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

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