CORO1C is Associated With Poor Prognosis and Promotes Metastasis Through PI3K/AKT Pathway in Colorectal Cancer

Abstract

Trophoblast cell surface protein 2 (Trop2) is one of the cancer-related proteins that plays a vital role in biological aggressiveness and poor prognosis of colorectal cancer (CRC). The study of the Trop2 related network is helpful for us to understand the mechanism of tumorigenesis. However, the effects of the related proteins interacting with Trop2 in CRC remain unclear. Here, we found that coronin-like actin-binding protein 1C (CORO1C) could interact with Trop2 and the expression of CORO1C in CRC tissues was higher than that in paracarcinoma tissues. The expression of CORO1C was associated with histological type, lymph node metastasis, distant metastasis, AJCC stage, venous invasion, and perineural invasion. The correlation between CORO1C expression and clinical characteristics was analyzed demonstrating that high CORO1C expression in CRC patients were associated with poor prognosis. Furthermore, CORO1C knockdown could decrease the cell proliferation, colony formation, migration and invasion in vitro and tumor growth in vivo. The underlying mechanisms were predicted by bioinformatics analysis and verified by Western blotting. We found that PI3K/AKT signaling pathway was significantly inhibited by CORO1C knockdown and the tuomr-promoting role of CORO1C was leastwise partly mediated by PI3K/AKT signaling pathway. Thus, CORO1C may be a valuable prognostic biomarker and drug target in CRC patients.

ATF2 loss promotes tumor invasion in colorectal cancer cells via upregulation of cancer driver TROP2

“…Interestingly, metastatic cells are rich in filopodia-like structures [ 34 ]. Recently, TROP2-interacting proteins were linked to matrix degradation, cell shape, motility, and invasion in CRC cells [ 35 ]. We found that under adhesion blockade, ATF2-KO cells built only vital single cells or small aggregates, and that transient TROP2 silencing attenuated this de-adhesive effect, which was accompanied by a loss in cell–cell protrusions.…”

Coronin1C Is a GDP-Specific Rab44 Effector That Controls Osteoclast Formation by Regulating Cell Motility in Macrophages

“…For example, primary fibroblasts derived from Coronin1C-deficient mice display impaired cell migration and protrusion formation through abnormal actin filaments, microtubules, and intermediate filaments [ 26 ]. The involvement of Coronin1C in migration, invasion, and metastatic abilities has been observed in various cancer cells, such as human gastric cancer cells [ 15 , 27 , 28 ], melanoma cells [ 29 ], breast cancer cells [ 30 , 31 ], hepatocellular carcinoma cells [ 32 ], glioblastoma cells [ 33 ]. Thus, the actin-binding protein Coronin1C is commonly involved in cell motility, including migration, invasion, and chemotaxis in many cell types.…”

Upregulation of ADAMDEC1 correlates with tumor progression and predicts poor prognosis in non‐small cell lung cancer (NSCLC) via the PI3K/AKT pathway

“…Proteins involved in the PI3K/Akt pathway are abnormally expressed in several tumors, thereby leading to the progression of breast, gastric, nasal and pancreatic cancers, among others 35–37 . This pathway is closely associated with tumor proliferation, autophagy and migration 38–40 . Therefore, research on ADAMDEC1 and whether it targets the PI3K/AKT pathway may have great significance in the management of NSCLC.…”

“… 35 , 36 , 37 This pathway is closely associated with tumor proliferation, autophagy and migration. 38 , 39 , 40 Therefore, research on ADAMDEC1 and whether it targets the PI3K/AKT pathway may have great significance in the management of NSCLC. Here, we demonstrate that PI3K/AKT is critically involved in the regulation of ADAMDEC1 expression to maintain cancer cell survival and proliferations.…”