Abnormal expression of TRIB3 in colorectal cancer: a novel marker for prognosis

Abstract

BACKGROUND: TRIB3 is a human homologue of Drosophila tribbles. Previous studies have shown that TRIB3 controls the cell growth through ubiquitination-dependent degradation of other proteins, whereas its significance in the prognosis of colorectal cancer (CRC) is not yet fully understood. MATERIALS: This study comprised 202 patients who underwent surgery for CRC, as well as 22 cell lines derived from human gastrointestinal cancer. The correlation of gene expression with clinical parameters in patients was assessed. The biological significance was evaluated by knockdown experiments in seven colorectal cancer cell lines. RESULTS: A total of 20 cancer cell lines (90.9%) expressed the TRIB3 gene. The assessment in surgical specimens indicated that the gene expression was significantly higher in the cancerous region than in the marginal non-cancerous region. Patients with high TRIB3 expression were statistically susceptible to a recurrence of the disease, and showed poorer overall survival than those with low expression. The assessment of TRIB3 knockdown in five cell lines showed that small interfering RNA (siRNA) inhibition resulted in a statistically significant reduction in cell growth. CONCLUSION: These data strongly suggest the usefulness of TRIB3 as a marker for predicting the prognosis of CRC patients, showing a basis for the development of effective treatments for CRC.

TRB3 reverses chemotherapy resistance and mediates crosstalk between endoplasmic reticulum stress and AKT signaling pathways in MHCC97H human hepatocellular carcinoma cells

“…The level of TRB3 mRNA expression was previously demonstrated to be altered in various tumor tissues including liver cancer tissue samples from patients and HCC cell lines (HepG2, Hep3B, Huh-7, HLE and HCF) compared with normal cell lines (12). The present study demonstrated an elevated expression level of TRB3 in MHCC97H cells, ~3.8-fold compared with the expression in the L-02 normal hepatic cell line (Fig.…”

“…A previous study revealed that TRB3 was highly expressed in a number of HCC cell lines under normal conditions or ER stress (12). To the best of our knowledge, the present study identified the first time that the target gene TRB3 is overexpressed in MHCC97H HCC cells in normal conditions.…”

“…TRB3 has been recognized as an oncogene for various types of tumor, including breast cancer, colorectal cancer, giloma, oral tongue squamous cell carcinoma and HCC (12)(13)(14)(15)(16). A previous study revealed that TRB3 was highly expressed in a number of HCC cell lines under normal conditions or ER stress (12).…”

The New Antitumor Drug ABTL0812 Inhibits the Akt/mTORC1 Axis by Upregulating Tribbles-3 Pseudokinase

“…Some laboratories reported elevated TRIB3 mRNA levels which correlated with bad prognosis in colorectal cancer (46) and breast cancer patients (47). On the other hand, high TRIB3 protein levels have been associated with good prognosis sensitivity to radiotherapy in breast cancer patients (48).…”

Developmental roles of tribbles protein family members

“…In melanomas, Trib2 facilitates growth and survival by down-regulating FOXO activity (Zanella et al, 2010). Trib levels are increased in lung cancers (Grandinetti et al, 2011), breast cancers (Wennemers et al, 2011a,b), B-cell chronic lymphocytic leukemia (B-CLL Johansson et al, 2010), and cancers of the esophagus and colon (Miyoshi et al, 2009). Because Trib3 is induced in tumors experiencing stress/ starvation conditions, it may contribute to the ability of cells to grow under the nutrient limiting conditions typical within a tumor (Bowers et al, 2003;Schwarzer et al, 2006).…”