Abstract
Calponin 3 (CNN3) is an F-actin-binding protein that regulates actin cytoskeletal rearrangement. However, the role of CNN3 in cancer cell invasion and resistance to chemotherapeutic agents has not yet been investigated. The present study was undertaken to investigate whether CNN3 influences cancer-related phenotypes in gastric cancer. We demonstrate that CNN3 contributes to cell invasion and resistance to doxorubicin in gastric cancer. CNN3 expression was markedly elevated in highly invasive cancer cell lines compared to less invasive or noninvasive cancer cell lines. Depletion of CNN3 protein suppressed the invasive ability of gastric cancer cells. The highly invasive MKN-28 gastric cancer cells were more resistant to doxorubicin than the noninvasive MKN-45 cells; however, knockdown of CNN3 expression in MKN-28 cells resensitized them to doxorubicin treatment. Taken together, our results suggest that CNN3 plays a key role in invasiveness and doxorubicin resistance in gastric cancer cells.
Highlights
Gastric cancer (GC) is the fifth most common cancer and the third leading cause of cancer-related mortality worldwide [1, 2]
We found a significant correlation between Calponin 3 (CNN3) expression and cancer cell invasiveness in gastric and breast cancer (BC) cells and we demonstrated that CNN3 can positively regulate invasiveness and doxorubicin resistance in GC cells
We found that the highly invasive BC cell line MDA-MB231 has higher levels of CNN3 mRNA compared to the noninvasive BC cell line MCF-7 (Figure 1(a), right)
Summary
Gastric cancer (GC) is the fifth most common cancer and the third leading cause of cancer-related mortality worldwide [1, 2]. The incidence of GC and mortality associated with this disease has gradually decreased in Japan and Korea, it still remains the second leading cause of death in Korea [3]. Despite advancements in our understanding of cancer mechanisms and improvement in cancer treatments over the last decade, metastasis remains the major cause of mortality in cancer patients. Doxorubicin (Dox) is a member of the anthracycline family of drugs and, along with other chemotherapy agents, such as mitomycin and 5-fluorouracil, constitutes the gold standard treatment in advanced GC patients [6]. Drug efflux pump inhibitors like cyclosporin A, ketoconazole, and verapamil add to the toxic side effects associated with doxorubicin treatment, decreasing the quality of life of cancer patients [15]. Dox must be coadministered with a chemotherapeutic agent that abrogates doxorubicin resistance and has no overlapping benefits or side effects
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