Trop2 inhibition suppresses the proliferation and invasion of laryngeal carcinoma cells via the extracellular signal-regulated kinase/mitogen-activated protein kinase pathway

Abstract

The cell surface glycoprotein Trop2 is overexpressed in various types of epithelial cancer. Laryngeal carcinoma is one of the most common types of head and neck cancer and in a previous study, the expression of Trop2 in laryngeal squamous cell carcinoma (LSCC) was identified as an independent prognostic factor. However, the biological significance of Trop2 in LSCC development remains unclear. In the current study, Trop2 protein expression in fresh LSCC tissue and paracancerous tissue was investigated using western blotting. Trop2 in the Hep2 laryngeal cell line was subsequently suppressed by transfection with small interfering RNA (siRNA). The effects of knockdown of Trop2 on cell viability, migration, invasiveness and ERK/MAPK pathway activity were investigated in the current study. The expression of Trop2 in fresh LSCC tissue was demonstrated to be significantly greater than that in paracancerous tissue. Trop2 expression was also identified to be required for proliferation, migration and invasiveness of Hep2 laryngeal carcinoma cells, as all were blocked by siRNA-mediated Trop2 inhibition. Notably, the ERK/MAPK signaling pathway and cell cycle factor, cyclin D1, were identified to be suppressed following the knockdown of Trop2 in Hep2 cells. These observations suggest that Trop2 serves an oncogenic role in LSCC and has potential as a therapeutic target.

TROP2 methylation and expression in tamoxifen-resistant breast cancer

“…TACSTD2 is overexpressed in many cancers and has been associated with disease progression, migration, recurrence, and increased proliferation [ 27 , 33 – 36 ]. In published cell culture experiments, knockdown of TACSTD2 inhibits growth in MCF7 (contrary to our findings) and colon cancer cells [ 20 ], fetal rat lung cells (fibroblasts) [ 28 ], fetal lung fibroblasts [ 27 ], cervical cancer cells [ 26 ], and laryngeal carcinoma cells [ 30 ]. However, there also is evidence of decreased TACSTD2 expression in cancer [ 20 , 23 , 43 , 44 ].…”

“…TROP2 is silenced by promoter methylation in some tumors and cancer cell lines (bile duct, lung and prostate) [ 22 – 24 ]. However, TROP2 expression has been associated with both inhibition of proliferation [ 22 , 23 ] and increased growth and metastasis [ 20 , 25 – 30 ]. The role of TROP2 in endocrine-resistant breast cancer has not been evaluated previously.…”

Tissue mechanics and expression of TROP2 in oral squamous cell carcinoma with varying differentiation

“…Human trophoblast cell surface antigen 2 (TROP2), also called tumor-associated calcium signal transduction-2 (TACSTD-2), is a surface glycoprotein encoded by TACSTD that has extracellular domains, a single transmembrane domain, and a short tail [ 4 , 5 ]. TROP2 is overexpressed in many human cancers, including ovarian [ 6 , 7 ], gastric [ 8 , 9 ], colorectal [ 10 ], pancreatic [ 11 ], and laryngeal cancers [ 12 ]. Inhibiting TROP2 expression has shown promise in clinical applications [ 13 , 14 ].…”

Tissue Mechanics and Expression of TROP2 in Oral Squamous Cell Carcinoma with Varying Differentiation

“…This protein is a surface glycoprotein, encoded by the TACSTD gene, with extracellular domains, a single transmembrane domain, and short tail [3,4]. TROP2 is overexpressed in many human cancers, including ovarian [5,6], gastric [7,8], colorectal [9], pancreatic [10], and laryngeal cancer [11], but underexpressed in overturning cancerous tissues [12,13]. TROP2 regulates carcinogenic properties and adhesion, invasion, and migration of cancers.…”