Mitotic centromere-associated kinesin is a novel marker for prognosis and lymph node metastasis in colorectal cancer

Abstract

Mitotic centromere-associated kinesin (MCAK) is a microtubule depolymerase that is essential for proper kinetochore -microtubule attachment during spindle formation. Overexpression of MCAK has been correlated with aggressive forms of carcinoma, resulting in poor prognosis of colorectal cancer. The purpose of this study was to quantify MCAK expression in malignant and benign colorectal tissues and to determine if MCAK expression levels correlate with clinicopathologic factors and prognosis in colorectal cancer patients. Paired colorectal tissue samples from tumours and the corresponding normal tissues were obtained from 120 patients with colorectal cancer who underwent surgical resection. The real-time reverse transcriptase-PCR and immunohistochemistry were used to analyse mRNA and protein expression status with respect to various clinicopathological factors. MCAK expression was higher in colorectal cancer tissue (Po0.01) than in corresponding normal tissue, and this elevated expression level was markedly associated with factors such as lymph node metastasis (P ¼ 0.0023), venous invasion (P ¼ 0.019), peritoneal dissemination (P ¼ 0.021) and Dukes' classification (P ¼ 0.0023). Patients with high MCAK mRNA expression also showed a far poorer survival rate than those with low MCAK mRNA expression (Po0.01). Elevated MCAK expression was an independent predictor of overall survival and lymph node metastasis. These data suggest that MCAK expression may serve as a good marker of prognosis and lymph node metastasis in colorectal cancer.

Functional analysis of phosphorylation of the mitotic centromere-associated kinesin by Aurora B kinase in human tumor cells

“…These data provide the first molecular indication for clinical studies, where an overexpression of MCAK was associated with lymphatic invasion and lymph node metastasis in gastric and colorectal cancer patients. 18,19 Further investigations are required to explore the molecular mechanisms by which overexpression of MCAK increases mobility and invasiveness in cancer cells.…”

“…In support of this notion, overexpression of MCAK associates with a more invasive and metastatic phenotype and poor prognosis for breast, gastric and colorectal cancer patients. [17][18][19][20] Aurora B is the major regulator of MCAK by phosphorylating several residues. 11,[21][22][23] Previous studies in Xenopus leavis extracts and HeLa cells have reported that Aurora B decreases the catalytic activity of XKCM1, the Xenopus homolog of MCAK, and its localization to the kinetochore region by phosphorylating multiple residues, including serine 196 (S196).…”

Dynein regulates cell migration depending on substrate rigidity

“…In addition, dynein is also known to be a critical regulator of cancer motility and metastasis (13,14). Therefore, we examined the possibility that dynein can control cell migration when myosin activity is absent using a pharmacological inhibitor of dynein, EHNA, which is known to inhibit dynein-microtubule binding by suppression of the ATPase activity of dynein (15).…”

The role of kinesin family proteins in tumorigenesis and progression

“…This elevated expression was associated with lymph node metastasis, venous invasion, and peritoneal dissemination of colorectal cancer cells. 88,89 Again, The expression of MCAK mRNA in patients with colorectal cancer was related to a much poorer survival rate than that in patients who had low levels of MCAK mRNA expression. 89 Furthermore, the suppression of MCAK expression in breast cancer cells inhibited tumor growth.…”

“…88,89 Again, The expression of MCAK mRNA in patients with colorectal cancer was related to a much poorer survival rate than that in patients who had low levels of MCAK mRNA expression. 89 Furthermore, the suppression of MCAK expression in breast cancer cells inhibited tumor growth. 90 These findings suggest that targeting the MCAK gene may effectively control human cancers and that the detection of MCAK expression could be used as a tumor biomarker for early diagnosis or prognosis.…”