THBS2 promotes cell migration and invasion in colorectal cancer via modulating Wnt/β‐catenin signaling pathway

Abstract

Colorectal cancer (CRC) is the most common human digestive malignancy with a poor prognosis; the pathophysiology of colon cancer involves multiple linkages of regulatory networks. Recently, thrombospondin 2 (THBS2) has been extensively studied for its role in cancer progression. In this study, we evaluated the expression of THBS2 in CRC tissues and studied the possible mechanism by which THBS2 regulates CRC progression. Our results showed that the upregulation of THBS2 in CRC tissues and CRC cell lines and high expression of THBS2 was correlated with poor overall survival. The in vitro experimental data showed that THBS2 overexpression promoted CRC cell growth, invasion, and migration, while THBS2 inhibition exerted tumor‐suppressive actions on CRC cells. THBS2 knockdown suppressed the activity of Wnt/β‐catenin signaling. Collectively, the results implied that THBS2 exerted promotional effects on CRC cell proliferation, invasion, and migration, partly by modulating the Wnt/β‐catenin signaling pathway.

Identification of BGN and THBS2 as metastasis‐specific biomarkers and poor survival key regulators in human colon cancer by integrated analysis

“…55 THBS2 promotes CRC cells migration and invasion by regulating the Wnt/beta-catenin signalling pathway. 47 In our result, knockdown BGN or THBS2 significantly increased the proliferation inhibitory effect on CRC cells induced by 5-FU and oxaliplatin treatment. Thus, to improve the poor outcomes of CRC patients with metastasis, it may be therapeutically useful to consider ways suppress THBS2 or BGN expression in CRC and combine this with 5-FU treatment as a combination treatment strategy.…”

“…Meanwhile, BGN is overexpressed in colon cancer stem cells and activates NF‐κB pathway, which leads to chemotherapy resistance, 54 and BGN knockdown enhanced the HT‐29 cells' sensitivity to 5‐FU treatment 55 . THBS2 promotes CRC cells migration and invasion by regulating the Wnt/beta‐catenin signalling pathway 47 . In our result, knockdown BGN or THBS2 significantly increased the proliferation inhibitory effect on CRC cells induced by 5‐FU and oxaliplatin treatment.…”

“…It interacts with MMPs and matrix serine proteases like plasminogen activator to limit tumour growth and angiogenesis in a variety of malignancies, and it is recognized as a key ECM‐modifying enzyme. 51,52 THBS2 has been identified as a potential biomarker with clinical prognosis in CRC, 44,45 and the patients with positive THBS2 expression had a significantly lower likelihood of liver metastasis, 46 and up‐regulated was linked to poor overall survival 47 . THBS2 promotes CRC cells migration and invasion by regulating the Wnt/beta‐catenin signalling pathway and enhances aerobic glycolysis by regulating HIF‐1a 47 and thus contributes to CRC progression 48 .…”

Characterization of butyrate-metabolism in colorectal cancer to guide clinical treatment

“…CRC aggressiveness is triggered by SERPINE1 activation by ARNTL2 and circadian rhythm variations in circulating PAI-1 levels 44 . CRC cells migrate and invade more rapidly when THBS2 regulates the Wnt/β-linked protein signaling pathway 45 . It has been reported that COMP promotes cell proliferation during the early stages of colon cancer tumorigenesis 46 .…”

Comparative transcriptomic analysis and mechanistic characterization revealed the use of formononetin for bladder cancer treatment

“…58 A similar finding was observed by Qu et al that THBS2 promoted cell migration and invasion in colorectal cancer through the regulation of the Wnt/β-catenin signaling pathway. 59 In addition, THBS2 is more highly expressed in gastric cancer than in cancer-adjacent tissues. 60 Therefore, formononetin reduced the expression of all these targets, which could be one of the major regulatory mechanism of the observed decrease in the proliferation and migration of bladder cancer cells.…”