title: Myeloid cell leukemia-1 is associated with tumor progression by inhibiting apoptosis and enhancing angiogenesis in colorectal cancer.
abstract: Myeloid cell leukemia-1 (Mcl-1) is a highly expressed anti-apoptotic Bcl-2 protein in cancer. Therefore, inhibition of its expression induces apoptosis in cancer cells and enhances sensitivity to cancer treatment. The aims of this study were to evaluate whether Mcl-1 affects the oncogenic behaviors of colorectal cancer cells, and to document the relationship of its expression with various clinicopathological parameters in colorectal cancer. Mcl-1 knockdown induced apoptosis by activating cleaved caspase-3 and -9, and increasing the expression of the pro-apoptotic protein, PUMA. Mcl-1 knockdown induced cell cycle arrest by decreasing cyclin D1, CDK4 and 6, and by increasing p27 expression. Mcl-1 knockdown decreased both endothelial cell invasion and tube formation, and decreased the expression of VEGF. The phosphorylation level of STAT3 was decreased by Mcl-1 knockdown. The mean apoptotic index value of Mcl-1 positive tumors was significantly lower than that of Mcl-1 negative tumors. The mean microvessel density value of Mcl-1 positive tumors was significantly higher than that of negative tumors. Mcl-1 expression was significantly increased in colorectal cancer, also associated with tumor stage, lymph node metastasis, and poor survival. These results indicate Mcl-1 is associated with tumor progression through its inhibition of apoptosis and enhancement of angiogenesis in colorectal cancer.
authors: Department of Internal Medicine, Chonnam National University Medical School Gwangju, Republic of Korea.
authors: Wan-Sik
authors: WS
authors: Lee
authors: Department of Internal Medicine, Chonnam National University Medical School Gwangju, Republic of Korea.
authors: Young-Lan
authors: YL
authors: Park
authors: Department of Internal Medicine, Chonnam National University Medical School Gwangju, Republic of Korea.
authors: Nuri
authors: N
authors: Kim
authors: Department of Internal Medicine, Chonnam National University Medical School Gwangju, Republic of Korea.
authors: Hyung-Hoon
authors: HH
authors: Oh
authors: Department of Internal Medicine, Chonnam National University Medical School Gwangju, Republic of Korea.
authors: Dong-Jun
authors: DJ
authors: Son
authors: Department of Internal Medicine, Chonnam National University Medical School Gwangju, Republic of Korea.
authors: Mi-Young
authors: MY
authors: Kim
authors: Department of Internal Medicine, Chonnam National University Medical School Gwangju, Republic of Korea.
authors: Chan-Young
authors: CY
authors: Oak
authors: Department of Internal Medicine, Chonnam National University Medical School Gwangju, Republic of Korea.
authors: Cho-Yun
authors: CY
authors: Chung
authors: Department of Internal Medicine, Chonnam National University Medical School Gwangju, Republic of Korea.
authors: Hyung-Chul
authors: HC
authors: Park
authors: Department of Internal Medicine, Chonnam National University Medical School Gwangju, Republic of Korea.
authors: Jong-Sun
authors: JS
authors: Kim
authors: Department of Internal Medicine, Chonnam National University Medical School Gwangju, Republic of Korea.
authors: Dae-Seong
authors: DS
authors: Myung
authors: Department of Internal Medicine, Chonnam National University Medical School Gwangju, Republic of Korea.
authors: Sung-Bum
authors: SB
authors: Cho
authors: Department of Internal Medicine, Chonnam National University Medical School Gwangju, Republic of Korea.
authors: Hyun-Soo
authors: HS
authors: Kim
authors: Department of Internal Medicine, Chonnam National University Medical School Gwangju, Republic of Korea.
authors: Young-Eun
authors: YE
authors: Joo
keywords: Myeloid cell leukemia-1; angiogenesis; apoptosis; colorectal neoplasm; prognosis
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