Overexpression of crkl correlates with poor prognosis and cell proliferation in non‐small cell lung cancer

Wang, Yan; Dong, Qianze; Fu, Ling; Stoecker, Maggie; Wang, Endi; Wang, Enhua

doi:10.1002/mc.21935

Cited by 37 publications

(36 citation statements)

References 23 publications

(30 reference statements)

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“…Overexpression of CRKL is found in NSCLC and is associated with poor tumor differentiation, AC, advanced p-TNM stage, high proliferation index and poor overall survival. In addition, overexpression of CRKL in cell lines promotes cell proliferation by facilitating cell cycle progression (56). In the current study, the CRKL protein level was not demonstrated to be significantly associated with clinical features such as gender, smoking history, clinical staging, EGFR status and ALK status.…”

Section: A B C Dcontrasting

confidence: 72%

Expression level of CRKL and AXL combined with exon 19 deletion in EGFR and ALK status confer differential prognosis of lung adenocarcinoma subtypes

Cai

Dong

et al. 2016

Oncology Letters

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Abstract. Non-small cell lung cancer (NSCLC) is a lethal cancer-related disease in population. Adenocarcinoma (AC) is subclassified into several subtypes based on the new classification by the International Association for the Study of Lung Cancer, American Thoracic Society and European Respiratory Society in 2011. Correlation between original expression of Crk-like (CRKL) and anaplastic lymphoma receptor tyrosine kinase in diverse histological components of AC and epidermal growth factor receptor (EGFR) or ALK status was evaluated by immunohistochemistry and sequencing in present study. A total of 106 cases, including 83 patients (78.3%) with mixed-type ACs, were assessed in the present study using eligible follow-up data. The ACs consisted of 32 acinar, 12 papillary, 5 mucinous, 11 micropapillary and 46 solid-predominant ACs. In total, 69.8% samples were composed of 2 or 3 histological components, with different expression levels of CRKL and AXL. ACs with EGFR mutation had a higher level of AXL expression compared with ACs without mutation (P=0.019). Multivariate survival analysis showed that AC subtypes and EGFR mutation subtypes were significantly associated with the progression-free survival (PFS) time. Acinar AC was the subtype with the most notable PFS time (30.6 months), which was significantly different from the PFS time of papillary, mucinous, micropapillary and solid-predominant ACs (hazard ratio, 0.4; 95% CI, 0.21-0.75; P=0.005). Among the ACs with exon 19 mutation, the median PFS time (28.8 months) of patients with a lower level of AXL protein expression was increased compared with the PFS time of patients with the L858R mutation and wild-type EGFR (9.1 months and 11 months, respectively; P=0.03), whereas no significant difference in ACs with an increased level of AXL expression. However, AC patients with higher level of CRKL expression had better PFS (28.8 months) than patients with the L858R mutation and wild-type EGFR (9.1 months and 11.3 months, respectively). Exon 19 deletion is an important status that is associated with an improved response to conventional chemotherapy. The identification of EGFR mutations combined with CRKL and AXL status may potentially alter the way that lung AC is treated.

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Section: A B C Dcontrasting

confidence: 72%

Expression level of CRKL and AXL combined with exon 19 deletion in EGFR and ALK status confer differential prognosis of lung adenocarcinoma subtypes

Cai

Dong

et al. 2016

Oncology Letters

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“…In recent decades, the biological roles of CCL20/CCR6 axis in progression and metastasis of gastric cancer were not well featured. In addition, CrkL acts as an adaptor protein to induce the intracellular signal transduction [8,9]. As reported, CrkL is also highly expressed in different cancer cells, such as gastric cancer, glioblastoma, hepatocellular carcinoma, and implicated in the aggressiveness and transformation of malignance [10,11].…”

Section: Introductionmentioning

confidence: 84%

CrkL meditates CCL20/CCR6-induced EMT in gastric cancer

Han

Wu²,

Yang³

et al. 2015

Cytokine

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“…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.…”

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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Overexpression of crkl correlates with poor prognosis and cell proliferation in non‐small cell lung cancer

Cited by 37 publications

References 23 publications

Expression level of CRKL and AXL combined with exon 19 deletion in EGFR and ALK status confer differential prognosis of lung adenocarcinoma subtypes

Expression level of CRKL and AXL combined with exon 19 deletion in EGFR and ALK status confer differential prognosis of lung adenocarcinoma subtypes

CrkL meditates CCL20/CCR6-induced EMT in gastric cancer

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

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