Involvement of FAK-ERK2 signaling pathway in CKAP2-induced proliferation and motility in cervical carcinoma cell lines

Abstract

Cervical carcinoma is the fourth most common cause of death in woman, caused by human papillomavirus (HPV) infections and arising from the cervix. Cytoskeleton-associated protein 2 (CKAP2), also known as tumor-associated microtubule-associated protein, has been linked to tumorigenic effects. In the present study, we screened CKAP2 as a new candidate gene which promotes development of cervical carcinoma, in two independent datasets (TCGA and GSE27678). Results showed that CKAP2 expression was significantly up-regulated in cervical cancerous tissues compared with normal counterparts. Gene set enrichment analysis (GSEA) showed that metastasis, cell cycle and FAK pathways were related with elevated CKAP2 expression. Knockdown of CKAP2 expression significantly inhibited cell proliferation, migration and invasion both in HeLa and C-33A cells. And depletion of CKAP2 down-regulated the expression of metastasis and cell cycle related proteins as well as the phosphorylation of ERK2 (p-ERK2), except E-cadherin. In vivo experiment revealed that knockdown of CKAP2 inhibited C-33A cells proliferation. However, FAK inhibitor PF-562271 and ERK2 inhibitor VX-11e treatment significantly inhibited CKAP2 overexpression-induced cell proliferation, migration and invasion in SiHa cells. In conclusion, our study suggests that CKAP2 acts as a functional oncogene in cervical carcinoma development and may exert its function by targeting FAK-ERK2 signaling pathway.

JAM-A knockdown accelerates the proliferation and migration of human keratinocytes, and improves wound healing in rats via FAK/Erk signaling

“…These findings overall suggest that loss of JAM-A promotes keratinocyte proliferation and migration, and the in vivo healing course, which is regulated by the signaling of FAK-mediated Erk1/2 activation. It is worthy to note that although the half-life of PF-562271 or PD98059 is not specified by the manufacturer, the working concentration and treatment duration regarding these two drugs are selected with great caution based on several important literatures 16 , 17 , 24 , 25 and our pilot experiments. The optimum concentration and treatment duration of JAM-A siRNA duplexes were also carefully selected based on our previously published works 26 and preliminary data, we found that transfection of keratinocytes with 100 nM JAM-A siRNA duplex (50 nM seq#1 + 50 nM seq#2, see Supplemental Fig.…”

Identification of Core Genes Involved in the Progression of Cervical Cancer Using an Integrative mRNA Analysis

“…In this study, CKAP2 has been observed to have an oncogenic function in CC development, based on TCGA data, and this is likely accomplished via its interference with FAK-ERK2 signaling [ 44 ]. Another gene detected in this study to be involved in CC pathogenesis is DUOX1.…”

CKAP2 expression is associated with glioma tumor growth and acts as a prognostic factor in high‑grade�glioma

“…In a previous study of early-stage breast cancer, high CKAP2 expression was revealed to promote the proliferation of tumor cells and significantly shorten relapse-free survival ( 17 ). Additionally, overexpression of CKAP2 activates the focal adhesion kinase (FAK)-extracellular signal-regulated kinase 2 signaling pathway, and induces cell proliferation and migration; however, this effect can be blocked by FAK inhibitors ( 18 ). In addition to CKAP2, other members of the CKAP family have also demonstrated similar effects on tumor cells, including CKAP4.…”

“…CKAP2 was recently reported to be a substrate of cyclin-dependent kinase (CDK)1-cyclin B and was indicated to be essential for bipolar spindle formation ( 14 ). The oncogenic nature of CKAP2 in the occurrence and development of gastric ( 15 ), ovarian ( 16 ) and breast cancer ( 17 ), and other malignant tumors ( 18 – 21 ) has been elaborated. However, limited studies have assessed the biological characteristics and significance of CKAP2 in HGG.…”