CSE1L/CAS, the cellular apoptosis susceptibility protein, enhances invasion and metastasis but not proliferation of cancer cells.
BACKGROUND
The cellular apoptosis susceptibility (CAS) protein is regarded as a proliferation-associated protein that associates with tumour proliferation as it associates with microtubule and functions in the mitotic spindle checkpoint. However, there is no any actual experimental study showing CAS (or CSE1 and CSE1L) can increase the proliferation of cancer cells. Previous pathological study has reported that CAS was strongly positive stained in all of the metastasis melanoma that be examined. Thus, CAS may regulate the invasion and metastasis of cancers. CAS is highly expressed in cancers; if CAS is associated with cancer proliferation, then increased CAS expression should be able to increase the proliferation of cancer cells. We studied whether increased CAS expression can increase cancer cell proliferation and whether CAS regulates the invasion of cancer cells.


METHODS
We enhanced or reduced CAS expression by transfecting CAS or anti-CAS expression vectors into human MCF-7 breast cancer cells. The proliferations of cells were determined by trypan blue exclusion assay and flow cytometry analysis. Invasion of cancer cells were determined by matrigel-based invasion assay.


RESULTS
Our studies showed that increased CAS expression was unable to enhance cancer cell proliferation. Immunofluorescence showed CAS was distributed in cytoplasm areas near cell membrane and cell protrusions. CAS was localized in cytoplasmic vesicle and immunogold electronmicroscopy showed CAS was located in vesicle membrane. CAS overexpression enhanced matrix metalloproteinase-2 (MMP-2) secretion and cancer cell invasion. Animal experiments showed CAS reduction inhibited the metastasis of B16-F10 melanoma cells by 56% in C57BL/6 mice.


CONCLUSIONS
Our results indicate that CAS increases the invasion but not the proliferation of cancer cells. Thus, CAS plus ECM-degradation proteinases may be used as the markers for predicting the advance of tumour metastasis.
Liao
Ching-Fong
CF
Institute of Cellular and Organismic Biology, Academia Sinica, Taipei, Taiwan, PR China. liao@gate.sinica.edu.tw
Luo
Shue-Fen
SF
Li
Li-Tzu
LT
Lin
Chuang-Yu
CY
Chen
Ying-Chun
YC
Jiang
Ming-Chung
MC
D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D029563:Cellular Apoptosis Susceptibility Protein / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D015151:Immunoblotting; D051379:Mice; D008810:Mice, Inbred C57BL; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology
D029563:Cellular Apoptosis Susceptibility Protein