CRKL overexpression promotes cell proliferation and inhibits apoptosis in endometrial carcinoma

Abstract

The v-Crk avian sarcoma virus CT10 oncogene homolog-like (CRKL) protein is important in cancer progression. However, its expression pattern and biological roles in human endometrial carcinoma remain unexplored. The potential mechanism of CRKL-induced cancer progression is still unclear. The present study aimed to explore the expression pattern and biological roles of CRKL in human endometrial carcinoma. Using immunohistochemistry, it was observed that the CRKL protein was overexpressed in 50.5% (44/87) of endometrial carcinoma tissues. Plasmid transfection of CRKL into Ishikawa cells was performed, and CRKL overexpression promoted cell proliferation, colony formation and cell cycle transition in the transfected cells. In addition, CRKL overexpression inhibited cell apoptosis in Ishikawa cells treated with cisplatin, with decreased caspase-3 and caspase-9 cleavage. Further analysis revealed that CRKL upregulated the expression of cyclin D1, cyclin E, B cell lymphoma (Bcl)-2 and survivin, and downregulated Bcl-2 associated X protein expression. In conclusion, the present study demonstrated that CRKL overexpression in endometrial carcinoma contributes to malignant cell growth and resistance to apoptosis, possibly through Bcl-2.

Copy number gains of the putative CRKL oncogene in laryngeal squamous cell carcinoma result in strong nuclear expression of the protein and influence cell proliferation and migration

“…Our recent study has demonstrated that CRKL (22q11) is seldomly but recurrently amplified in laryngeal squamous cell carcinoma 8 . Morover, CRKL is known to be overexpressed in a number of different cancer types, including these of breast 19,20 , gastric 21,22 , endometrial carcinoma 23 and lung 24,25 . Overepression of CRKL is also present in colorectal cancers 26 www.nature.com/scientificreports www.nature.com/scientificreports/ and cervical cancer samples 27 .…”

CRKL and CK2 <i>β</i> over Expression Are Independent Predictors of Patients Survival in Endometrioid Endometrial Carcinoma

“…Endometrioid carcinoma is the commonest subtype of endometrial carcinoma which is considered one of the commonest gynecological cancers worldwide [2]. Former researchers showed that disordered expression of certain proteins in endometrioid carcinoma tissues could contribute to its progression and malignant behavior [2], but novel bio-markers which are responsible for malignant initiation and progression and that which predict the aggressive behavior have been still urgently needed aiming at discovering novel targeted therapy. CRKL protein was found to be upregulated in many cancers, moreover, CRKL amplification was observed in bronchogenic carcinoma, colorectal cancer and pancreatic cancer [2].…”

“…We have incubated sections which were cut and put on positively charged slides with anti-CRKL rabbit polyclonal antibody ( The intensity of both CRKL and CK2 β staining was given scores from 0 -3; 0 Open Journal of Obstetrics and Gynecology The scores of each tumor sample have been multiplied to reach a final stain score of zero-12. We consider 5 as a cut point to differentiate between CRKL and CK2 β low expression which is less than 5 total stain score and tumor samples scoring 5 -12 were considered to exhibit CRKL and CK2 β overexpression [2]. Stratification of RFS, PFS, DMFS, and OS was done according to CRKL and CK2 β expression.…”

“…So, it is important to discover new biomarkers that can guide physicians to plan treatment for individual patients who are highly needed. Identifying molecular mediators which are conferring more malignant potential to cells of endometrial carcinoma could be used as novel predictive tumor biomarkers for the risk of progression of endometrial carcinoma [2]. V-Crk avian sarcoma virus CT10 oncogene homolog-like (CRKL) is an adapter proteins family member of the CRK; that has many biological roles, like cell proliferation, adhesion, migration, cell cycle progression, cell survival, and cell invasiveness [3].…”

“…V-Crk avian sarcoma virus CT10 oncogene homolog-like (CRKL) is an adapter proteins family member of the CRK; that has many biological roles, like cell proliferation, adhesion, migration, cell cycle progression, cell survival, and cell invasiveness [3]. CRKL protein was reported to be dysregulated in many malignant cancers [2]. But, its expression pattern in tumor cells, its biological and clinical roles in endometrial carcinoma patients remain uncertain.…”