Page 89 - D. Cancer biology

[D-59]
Downregulation of ACSM3 promotes tumorigenesis in breast cancer.
Hong-Beum Kim
Department of Premedical Course, Chosun University School of Medicine, 309 Pilmun-daero, Dong-gu,

Gwang-ju 61452,Republic of Korea

Abstract Breast cancer is one of the most common cancer diagnosed worldwide. However, the detailed molecular mechanisms
underlying antitumor activity in breast cancer remains largely unknown. Acyl-CoA medium-chain synthetase 3 (ACSM3) is an
acyl-CoA synthetase which form an activating thioester linkage between the fatty acid and CoA. We investigated the biological
function and clinical implications of ACSM3 in breast cancer. We revealed ACSM6-mediated gene expression profile in breast
cancer cells using RNA-Sequencing. We found that ACSM3 expression was significantly decreased in tumors (75%) compared
to normal. Migration & invasion assay and soft agar assays were carried out for functional analysis in vitro and a xenograft
model was used to analyze the effects of ACSM3 on cancer growth in vivo. Overexpression of ACSM3 attenuated migration
and invasion of breast cancer cells in vitro and upregulated the phosphorylation of AKT. Our study indicates that ACSM3
suppresses cell growth, migration and invasion by directly upregulating WNT/AKT-pathway in breast cancer, acting as a tumor
suppressor. Our study also suggests that ACSM3 may serve as a potential therapeutic target for patients in breast cancer.

Result

Figure 1. ACSM3 expression was low in all the
breast cancer cell lines, as shown by western
blotting. However normal MCF10A cell Figure 5. ACSM3 expressing MDA-MB-231
expressed high ACSM3 level.
cells were injected subcutaneously into the right
flank of 5-week-old nude mice and tumor
Figure 3. Representative images and quantitative volume was assessed every 2 to 5 days for 20
5
results of soft agar assay in MDA-MB-231 and T47D days. 3X 10 MDA-MB-231/ control vector and
cells with ACSM3 overexpression and control . Each control vector-transfected MDA-MB-
value shown represents the mean ± S.D. from three 231/ACSM3 cells were also injected as controls.
s ep a r at e ex p er i m e n t s . ** , P < 0 . 01 . Data are presented as the mean ± S.D. three
ex p e r i m en t s . . **, P < 0 . 01 .

Figure 2. Representative images and quantitative Figure 4. Overexpression of ACSM3 inhibits
results of migration in MDA-MB-231 and T47D cells colorectal metastasis via the phosphorylation of
with ACSM3 overexpression and control .Each value AKT. A: Results of phospho-kinase array
shown represents the mean ± S.D. from three suggested that activities of AKT were inhibited in
s e p ar at e ex p er i m e n t s . * *, P < 0 . 01 . MDA-MB-231/ACSM3 cells. B: Impacts of Figure 6. ACSM3 expression in human breast
ACSM6 overexpression on the activity AKT were cancer-normal tissues detected by
d et ec t ed by w es t er n b lo t a ssa y . immunohistochemical assay. Brown staining
indicates positive ACSM3 staining.
Conclusion 1. ACSM3 suppresses cell growth, migration, invasion, anchorage independent and Xenograft by directly
downregulating WNT/AKT-pathway in breast cancer.
2. ACSM3 is downregulated in breast cancer patients tissues.
3. ACSM3 is a novel prognostic marker and potential therapeutic target for breast cancer.

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