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Metastasis-Associated in Colon Cancer-1 Associates With Poor Prognosis and Promotes Cell Invasion and Angiogenesis in Human Cervical Cancer
  1. Xiang Zhou, PhD*,
  2. Chang-Juan Xu, PhD,,
  3. Jun-Xian Wang, PhD,§,
  4. Ting Dai, PhD*,
  5. Ya-Ping Ye, PhD,
  6. Yan-Mei Cui, PhD,
  7. Wen-Ting Liao, PhD,
  8. Xin-Lin Wu, PhD§ and
  9. Jian-Ping Ou, PhD
  1. *Department of Microscurgery and Hand Surgery, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China;
  2. Department of Pathology of Basic Medical Sciences, Southern Medical University, Guangzhou, China; and
  3. Department of Gynaecology and Obstetrics, the 157 Affiliated Hospital, General Hospital of Guangzhou Military Command of PLA, Guangzhou, China;
  4. §Department of Traditional Chinese Medicine, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; and
  5. Center for Reproductive Medicine, the Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
  1. Address correspondence and reprint requests to Jian-Ping Ou, PhD, Center for Reproductive Medicine, the Third Affiliated Hospital, SunYat-sen University, Guangzhou 510630, China. E-mail: dr.oujianping@gmail.com; Xin-Lin Wu, PhD, Department of Traditional Chinese Medicine, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China. E-mail: wxl3pro@163.com; Wen-Ting Liao, PhD, Department of Pathology, Nanfang Hospital and School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China. E-mail: liaowt2002@gmail.com.

Abstract

Objective The aim of this study is to investigate the clinicopathologic significance and potential role of metastasis-associated in colon cancer-1 (MACC1) in the progression of cervical cancer.

Methods MACC1 expression was examined in cervical cancer cell lines, 6 matched cervical cancer tissues, and adjacent noncancerous tissues using Western blotting and real-time reverse transcriptase polymerase chain reaction. MACC1 protein expression and localization were determined in 181 paraffin-embedded archived cervical cancer samples using immunohistochemistry. Statistical analyses were applied to evaluate the clinicopathologic significance. The effects of MACC1 on cell migration, invasion, and angiogenesis were examined using migration assay, wound healing assay, 3-dimensional morphogenesis assay, and chicken chorioallantoic membrane assay. Western blotting was performed to examine the impact of MACC1 on the Akt and nuclear factor κB signaling pathways.

Results Both protein and messenger RNA levels of MACC1 was up-regulated in cervical cancer cell lines and cervical cancer tissues, as compared with normal tissues. High MACC1 expression was detected in 96 (53%) of 181 of the cervical cancer tissues. In addition, high MACC1 expression correlated significantly with aggressiveness of cervical cancer, including International Federation of Gynecology and Obstetric stage (P = 0.001), pelvic lymph node metastasis (P = 0.004), recurrence (P = 0.037), and poor survival (P = 0.001). Moreover, enforced expression of MACC1 in cervical cancer cell lines significantly enhanced cell migration, invasion, and angiogenesis. Conversely, knockdown of MACC1 caused an inhibition of cell migration, invasion, and angiogenesis. Up-regulation of MACC1 increased, but knockdown of MACC1 decreased the expression of matrix metalloproteinase-2 and matrix metalloproteinase-9. Furthermore, enforced expression of MACC1 could enhance, but knockdown of MACC1 could reduce AKT and nuclear factor κB pathway activity.

Conclusions Our findings suggest that MACC1 protein, as a valuable marker of cervical cancer prognosis, plays an important role in the progression of human cervical cancer cells.

  • Cervical cancer
  • MACC1
  • Invasion
  • Angiogenesis
  • Akt
  • NF-κB

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Footnotes

  • Xiang Zhou and Chang-Juan Xu are equal contributors.

  • This study was supported by The National Natural Science Foundation of China (81172055); Guangdong Provincial Natural Science Foundation of China (S2012010009643); Zhu Jiang Science & Technology New Star Foundation in Guangzhou City (2012J2200052).

  • The authors declare no conflicts of interest.

  • Supplemental digital content is available for this article. Direct URL citation appears in the printed text and is provided in the HTML and PDF versions of this article on the journal’s Web site (www.ijgc.net).

  • This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially.

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