A metalloproteinase of the disintegrin and metalloproteinases and the ThromboSpondin Motifs 6 as a novel marker for colon cancer: functional experiments

Abstract

Herein, we aimed to investigate the functions of ADAMTS6 in colon cancer and its potential mechanism. Based on the data acquired from TCGA database, we revealed that ADAMTS6 was highly expressed in colon cancer tissues, and high expression of ADAMTS6 predicted worse prognosis in patients with colon cancer. Moreover, qRT-PCR demonstrated that the levels of ADAMTS6 were higher in colon cancer cell lines (NCI-H508, Caco-2, CW-2 and HCT 116) than that in normal control cell line CCD-18Co. Functional experiments displayed that depletion of ADAMTS6 repressed NCI-H508 cell growth, invasion and migration whilst overexpression of ADAMTS6 facilitated Caco-2 cell growth, invasion and migration. Moreover, ADAMTS6 silencing enhanced the protein expression of E-cadherin and reduced the levels of N-cadherin, Vimentin and Snail in NCI-H508 cells, whereas ADAMTS6 overexpression showed the counter effects in Caco-2 cells. The protein levels of p-AKT and p-p65 were decreased by depletion of ADAMTS6 in NCI-H508 cells, while their levels were enhanced by overexpression of ADAMTS6 in Caco-2 cells. These consequences indicated that the accelerating effect of ADAMTS6 on colon cancer cell growth, migration and invasion might be achieved by modulating EMT and AKT/NF-kB signaling pathway, offering important foundations for colon cancer treatment.

ADAMTS6: Emerging roles in cardiovascular, musculoskeletal and cancer biology

“…This dichotomy points to differing regulatory mechanisms and signaling pathways at work in colon and rectal cancer ( Li et al, 2012 ). A subsequent study, utilizing RNA-Seq data and qRT-PCR analysis, identified ADAMTS6 as highly expressed in colon cancer tissues and cell lines and was associated with cancer progression and predicted worse prognosis in colon cancer patients ( Wang et al, 2020 ). Knockdown of ADAMTS6 in a colon cancer cell line resulted in repression of colon cancer cell growth, invasion, and migration while overexpression led to the opposite.…”

“…Knockdown of ADAMTS6 in a colon cancer cell line resulted in repression of colon cancer cell growth, invasion, and migration while overexpression led to the opposite. This was in part mediated by the regulation of E-cadherin, N-cadherin, Vimentin, Snail p-AKT and p-p65 and point to the regulation of EMT and AKT/NFκB signaling pathways, respectively ( Wang et al, 2020 ). Therefore, ADAMTS6 might act as a catalyst for EMT in colon cancer progression thereby enhancing colon cancer cell growth, proliferation, migration, and invasion.…”

Role of the CTRP family in tumor development and progression (Review)

“…Treatment with LY294002, an inhibitor of Akt, reverses the induction effects of CTRP6 overexpression on ROS production, inflammation and extracellular matrix accumulation in mesangial cells. In addition, activation of the AKT/NF-κB pathway promotes the growth, migration and invasion of colon cancer cells ( 60 ). Because of these discrepancies, the specific underlying mechanisms of CTRP6 in colon cancer remain to be determined.…”