Crk and CrkL present with different expression and significance in epithelial ovarian carcinoma

Abstract

Adaptor protein Crk and CrkL were thought to be closely related because both consist of one SH2 and two SH3 domains and share 60% homology with the highest identity within their functional domains. Their functions were most presumed to be in part, if not all, redundant. And both were suggested to be implicated in carcinogenesis. In this study, both Crk and CrkL presented with much higher expression in ovarian cancer tissues than those in normal and benign ovarian tissues. However, in contrast with CrkL, high Crk expression displayed close association with advanced stages and high-grade diseases. Furthermore, the differential binding selectivity of Crk and CrkL to their downstream partners Dock 180 and C3G was demonstrated in ovarian cancer cell line SKOV3 through coimmunoprecipitation. Additionally, Crk-knockdown cells presented with changed morphology, reduced growth, and cell invasion but remained viable. In contrast, all CrkL-knockdown cells could not survive over time, gradually detaching from the bottom of plastic dish. In conclusion, these two highly homologous proteins hold features that allow for the differential association with each binding molecules, thereby activating different signaling pathways and being involved in diverse roles in ovarian cancer.

Knockdown of CkrL by shRNA deteriorates hypoxia/reoxygenation‐induced H9C2 cardiomyocyte apoptosis and survival inhibition Via Bax and downregulation of P‐Erk1/2

“…CrkL can regulate apoptosis and cell proliferation in the noncardiomyocytes. [16][17][18][19] Total knockout of CrkL 20 could lead to most of the mice to die before birth because of severe heart developmental abnormalities. It reminds that CrkL participates crucial roles in the development of embryonic heart.…”

CRKL plays a pivotal role in tumorigenesis of head and neck squamous cell carcinoma through the regulation of cell adhesion

“…Wang et al [18] reported that both CRK and CRKL presented with higher expression in ovarian cancer tissues than those in normal and benign ovarian tissue by immunohistochemical analysis. The detailed oncogenic function of CRKL including in vivo analysis in non-hematopoietic tumors has not been clarified.…”

CRKL knockdown promotes in vitro proliferation, migration and invasion, in vivo tumor malignancy and lymph node metastasis of murine hepatocarcinoma Hca-P cells

“…CRKL commonly localizes in multiple intracellular compartments mapped at 22q11.21 encoding a protein of 36 kDa [14]. CRKL deregulation is involved in the development and progression of a variety of cancers including gastric cancer (GC), glioblastoma multiforme (GBM), hepatocellular carcinoma (HCC), bladder cancer, lung cancer, colon cancer, ovarian cancer, leukemia, breast cancer, head and neck cancer, rhabdomyosarcoma and neuroblastoma [15][16][17][18][19][20][21][22]. Nevertheless, the role and action mechanism of CRKL in tumor progression are still unclear.…”