Cancer Res Treat.  2019 Jul;51(3):1207-1221. 10.4143/crt.2018.460.

KIF11 Functions as an Oncogene and Is Associated with Poor Outcomes from Breast Cancer

• Zhou J
• Chen WR
• Yang LC
• Wang J
• Sun JY
• Zhang WW
• He ZY
• Wu SG

• KMID: 2454312
• DOI: http://doi.org/10.4143/crt.2018.460

Abstract

PURPOSE
The study aimed to search and identify genes that were differentially expressed in breast cancer, and their roles in cancer growth and progression.
MATERIALS AND METHODS
The Gene Expression Omnibus (Oncomine) and The Cancer Genome Atlas databases (

Keyword

Breast neoplasms; KIF11; Survival; Oncogenes

MeSH Terms

AMP-Activated Protein Kinases
Animals
Apoptosis
Blotting, Western
Breast Neoplasms*
Breast*
Cadherins
Cell Survival
Gene Expression
Genome
Humans
In Vitro Techniques
Mice
Mice, Nude
Oncogenes*
Phosphorylation
Prognosis
Real-Time Polymerase Chain Reaction
Vimentin
Weights and Measures
AMP-Activated Protein Kinases
Cadherins
Vimentin

Figure

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  Fig. 1. Analysis of differentially expressed genes in patients with breast cancer. (A) Heat map of relative mRNA expression (normalized to tumor adjacent normal tissues) in patients with breast cancer, analyzed by the Oncomine database online tool. (B) Survival analyses of patients with breast cancer and different expression levels of LAGE3, KIF11, POP1, PARN, CCDC167, DDX39, NVL, and PPAPDC1A using the OncoLnc online survival analysis tool (http://www.oncolnc.org/).

• 

  Fig. 2. Relative expressions of KIF11 (A), POP1 (B), and PPAPDC1A (C) in 19 tumors.

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  Fig. 3. Expression analyses of KIF11, POP1, and PPAPDC1A in breast cancer based on The Cancer Genome Atlas. (A) The relative expression of KIF11, POP1, and PPAPDC1A in breast cancer versus non-paired tumor adjacent normal tissues. ****p < 0.0001. (B) The relative expressions of KIF11, POP1, and PPAPDC1A in breast cancer versus paired tumor adjacent normal tissues.

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  Fig. 4. Overall survival (OS) (A) and recurrence-free survival (RFS) (B) in patients with breast cancer by low and high KIF11, POP1, and PPAPDC1A expressions based on The Cancer Genome Atlas. HR, hazard ratio; CI, confidence interval.

• 

  Fig. 5. Analysis of KIF11 in breast cancer tissue and cells. (A) KIF11 expression in patients with breast cancer of grades I-1/II-A and II-B/III. (B) The relative background expressions of KIF11 in six breast cancer cell lines. (C) Both the BT549 and the MDA231 cell line were transduced with lentivirus (Lv003), siKIF11-1, or siKIF11-2 as negative controls, and the relative mRNA levels of KIF11 were detected by quantitative real-time polymerase chain reaction. (D) Protein levels of KIF11 in BT549 and MDA231 cells were detected by Western blotting. (E) Cell viability was evaluated by MTS in both BT549 and MDA231 cells. NC, cells transduced with empty Lv003 lentivirus; MOCK, cells without any treatment; siKIF11-2, cells transduced with siKIF11-2 lentivirus. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001.

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  Fig. 6. Downregulation of KIF11 influenced cell apoptosis, cell proliferation, cell migration, and invasion. (A) Cell apoptosis was determined by cytometry in KIF11-suppressed BT549 and MDA231 cells. (B) Cell proliferation of the KIF11-suppressed BT549 and MDA231 cells was assessed by clone forming assays. (C) Downregulation of KIF11 inhibited the cell migration and invasion capabilities of the BT549 and MDA231 cells. NC, normal control. *p < 0.05, **p < 0.01.

• 

  Fig. 7. Downregulation of KIF11 inhibited tumor growth in xenograft BALB/c nu/nu mice. (A) Appearance at 5-week post-implantation of BALB/c nu/nu mice xenografted with BT549 cells that had either normal (NC) or low KIF11 (siKIF) expression. (B) The tumor volume curve in each group between days 10 and 35 post-implantation. (C) The tumor weight in each group determined at 5 weeks after implantation. (D) Western blotting confirmed the downregulation of KIF11 in siKIF11 mice. (E) Representative image of hematoxylin and eosin showing the beneficial effect of KIF11 downregulation in breast tumors at 5-week post-implantation (magnification, 100×). GAPDH, glyceraldehyde 3-phosphate dehydrogenase. *p < 0.05, **p < 0.01, ****p < 0.0001.

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  Fig. 8. Representative Western blot showing the expressions of markers of epithelial-to-mesenchymal transition (EMT) and the associations of KIF11 with the classical cancer signaling pathways. (A) Markers of EMT (E-cadherin, N-cadherin, and vimentin) were measured by Western blot in both the siKIF11 or normal BT549 and MDA231 cells. (B) Multiple key signaling pathways components (ERK, AMPK, AKT, and CREB) were measured by western blot in both the siKIF11 or normal BT549 and MDA231 cells. Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) was used as the internal standard.

Reference

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