Metastasis-Associated in Colon Cancer-1 Associates With Poor Prognosis and Promotes Cell Invasion and Angiogenesis in Human Cervical Cancer.
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.
*Department of Microscurgery and Hand Surgery, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China; †Department of Pathology of Basic Medical Sciences, Southern Medical University, Guangzhou, China; and ‡Department of Gynaecology and Obstetrics, the 157 Affiliated Hospital, General Hospital of Guangzhou Military Command of PLA, Guangzhou, China; §Department of Traditional Chinese Medicine, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; and ∥Center for Reproductive Medicine, the Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Xiang
X
Zhou
Chang-Juan
CJ
Xu
Jun-Xian
JX
Wang
Ting
T
Dai
Ya-Ping
YP
Ye
Yan-Mei
YM
Cui
Wen-Ting
WT
Liao
Xin-Lin
XL
Wu
Jian-Ping
JP
Ou
D000230:Adenocarcinoma / Q000098:blood supply / Q000235:genetics / Q000473:pathology*; D014408:Biomarkers, Tumor / Q000502:physiology; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000098:blood supply / Q000235:genetics / Q000473:pathology*; D002465:Cell Movement; D049109:Cell Proliferation; D049033:Chorioallantoic Membrane / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D015996:Survival Rate; D015534:Trans-Activators; D014157:Transcription Factors / Q000502:physiology*; D014407:Tumor Cells, Cultured; D002583:Uterine Cervical Neoplasms / Q000098:blood supply / Q000235:genetics / Q000473:pathology*
D014408:Biomarkers, Tumor; C544162:MACC1 protein, human; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D015534:Trans-Activators; D014157:Transcription Factors