Calponin 3 Regulates Cell Invasion and Doxorubicin Resistance in Gastric Cancer

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.

Curcumin Treatment Identifies Therapeutic Targets within Biomarkers of Liver Colonization by Highly Invasive Mesothelioma Cells—Potential Links with Sarcomas

“…Calponin expression has been documented in several reports focusing on different types of sarcomas [ 28 , 29 ], leading to the conclusion that CNN3 is required for controlling proper contractility of the stress fiber network [ 27 ]. Two recent reports have confirmed the interest of this protein, revealing its key role in both invasiveness and drug resistance in gastric [ 30 ] and colon cancer cells [ 31 ]. Finally, among the correlations found between the seven M5-T1 tumor biomarkers and the 179 biomarkers of liver colonization, two interesting observations were the links between the increase in calponin 3 and prohibitin (PHB) and between the increase in nucleoporin (NUP53) and decrease in coronin 1A.…”

Calponin 3 suppresses proliferation, migration and invasion of non‑small cell lung cancer cells

“…The results of the in vitro cell function assay in the present study were also supported by the present findings that patients with LUAD in the high CNN3 expression group had a longer survival time than those in the low CNN3 expression group, according to Kaplan-Meier plotter results. CNN3 has been reported to serve a tumor-promoting role in osteosarcoma, gastric cancer and colon cancer ( 19 , 21 , 30 ). Actin cytoskeleton reorganization promotes cancer metastasis ( 31 ).…”

“…Furthermore, CNN3 expression is increased in cervical cancer cells, promoting the growth and metastasis of the disease ( 18 ). In gastric cancer, elevated CNN3 expression contributes to cancer cell resistance to doxorubicin ( 19 ). Additionally, CNN3 has been revealed to be a potential diagnostic marker of lymph node metastasis in colorectal cancer ( 20 ).…”

Noncoding RNAs in gastric cancer: implications for drug resistance

“…In gastric cancer patients, ADR is commonly used in combination with platinum drugs, 5-FU, VCR, PTX and mitomycin. Multiple genes and miRNAs have been shown to be responsible for the development of ADR resistance in gastric cancer [49][50][51][52][53].…”