Strong association of ARK5 with tumor invasion and metastasis
Abstract:
We recently identified a novel human AMPK family member, ARK5, and discovered that is a major factor in Akt-dependent cancer cell survival and migration activity through activation of MT1-MMPs in vitro. The mRNA expression of other AMPK family members and ARK5 was measured using RT-PCR in human colorectal carcinoma cell lines DLD-1, WiDr, HCT-15, SW620, LoVo, SW480, and mRNA expression of AMPK-alpha1, SNARK, MELK and ARK5, but not AMPK-alpha2, was detected in every line. Quantitative-PCR (Q-PCR) to estimate the amount of ARK5 mRNA expression in the cell lines showed that there is a variety of ARK5 expressions among the cell lines and high expression was observed in a cell line derived from the metastatic lesion, LoVo. To determine the effect of ARK5 overexpression on metastasis in vivo, we established human pancreas cancer cell line PANC-1 stably transfected with ARK5 full-length expression vector (P/ARK) and DLD-1 stably transfected with the same vector (D/ARK). Migration assay showed a remarkable increase in the activity both in P/ARK and D/ARK, and an in vivo metastasis assay showed a marked increase of P/ARK in liver metastasis. Based on these observations, it is suggested that ARK5 expression is involved in cancer invasion and metastasis.
Insights
The novel human AMPK family member ARK5 promotes cancer cell survival and migration. ARK5 overexpression enhances cancer cell invasion and metastasis, particularly in liver metastasis.
Area of Science:
- Molecular Biology
- Oncology
Background:
- A novel human AMP-activated protein kinase (AMPK) family member, ARK5, has been identified.
- ARK5 plays a role in Akt-dependent cancer cell survival and migration through MT1-MMP activation.
Purpose of the Study:
- To investigate the role of ARK5 in cancer cell invasion and metastasis.
- To analyze ARK5 mRNA expression in human colorectal carcinoma cell lines.
- To evaluate the effect of ARK5 overexpression on cancer metastasis in vivo.
Main Methods:
- RT-PCR and Quantitative-PCR (Q-PCR) were used to measure ARK5 mRNA expression in human colorectal carcinoma cell lines.
- Human pancreas and colorectal cancer cell lines were stably transfected with an ARK5 full-length expression vector.
- Migration and in vivo metastasis assays were performed to assess the impact of ARK5 overexpression.
Main Results:
- ARK5 mRNA was detected in all tested colorectal carcinoma cell lines, with varying expression levels.
- High ARK5 expression was observed in LoVo cells, derived from a metastatic lesion.
- Overexpression of ARK5 significantly increased migration activity in both pancreas and colorectal cancer cell lines.
- ARK5 overexpression markedly enhanced liver metastasis in vivo.
Conclusions:
- ARK5 expression is implicated in cancer cell invasion and metastasis.
- ARK5 may serve as a potential therapeutic target for inhibiting cancer spread.
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