TM4SF1 inhibits apoptosis and promotes proliferation, migration and invasion in human gastric cancer cells

Abstract

Gastric cancer (GC) is associated with poor patient prognosis, and so it crucial to investigate the molecular mechanisms underlying the progression of GC. The aim of the present study was to investigate the role of transmembrane-4 L6 family member 1 (TM4SF1) in the progression of GC. TM4SF1 small interfering RNA (siRNA) and TM4SF1-expressing plasmids were employed to regulate TM4SF1 expression. In vitro experiments were performed to determine the effect of TM4SF1 on the expression of apoptosis-associated molecules and determine the role of TM4SF1 in apoptosis, proliferation, migration and invasion using human GC cell lines MGC803 and MKN45. The data of the present study demonstrated that TM4SF1 may regulate the expression of apoptosis-associated molecules at the mRNA and protein levels. TM4SF1 silencing reduced B-cell lymphoma 2 (Bcl2) expression, whilst caspase-3 and Bcl2-associated X expression increased, and upregulating TM4SF1 reversed these changes in GC cells. Furthermore, TM4SF1 knockdown promoted apoptosis while inhibiting the proliferation, migration and invasion of GC cells. Rescue experiments demonstrated that TM4SF1 upregulation reversed the changes induced by transfection with TM4SF1 siRNA. In summary, TM4SF1 is an anti-apoptosis protein associated with the progression of GC. Additional in vivo experiments and clinical trials are required to confirm the possible use of TM4SF1 in tumor therapy.

Role of Transmembrane 4 L Six Family 1 in the Development and Progression of Cancer

“…In addition, silencing of TM4SF1 decreased the odds of lung and liver metastases in orthotopic pancreatic cancer (Cao et al, 2016). TM4SF1 also positively regulated the invasion and migration of human gastric cancer cells (Wei et al, 2018). TM4SF1 expression was higher in aggressively metastatic prostate cancer cells than in indolent, androgen-sensitive cancer cells (Chen et al, 2006).…”

“…Bcl2 inhibits apoptosis by preventing cytochrome c release from the mitochondria into the cytoplasm. Bax is a pro-apoptotic protein that forms a heterodimer with Bcl2 to suppress its function (Wei et al, 2018). In human gastric cancer, TM4SF1 increased cell proliferation and inhibited apoptosis by increasing Bcl2 expression and decreasing Bax expression (Wei et al, 2018).…”

“…Bax is a pro-apoptotic protein that forms a heterodimer with Bcl2 to suppress its function (Wei et al, 2018). In human gastric cancer, TM4SF1 increased cell proliferation and inhibited apoptosis by increasing Bcl2 expression and decreasing Bax expression (Wei et al, 2018). Moreover, TM4SF1 promoted the proliferation and growth of human bladder cancer cells in vitro and in vivo and inhibited apoptosis by decreasing the ratio of Bax/B-cell lymphoma xl (Bcl-xl) (Cao et al, 2018).…”

“…Caspase-3 and caspase-9 are critical apoptotic proteases ( Lossi et al, 2018 ). Overexpression of TM4SF1 significantly activated the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway, which acts through the downstream apoptosis-related proteins B-cell lymphoma 2 (Bcl2), BCL-2 associated X (Bax), caspase-3, and caspase-9 to induce anti-apoptotic effects in breast cancer ( Sun et al, 2015 ; Wei et al, 2018 ). Bcl2 and Bax are members of the Bcl2 family, which are key regulators of apoptosis ( Wang et al, 2020 ).…”

Overexpression of GSE1 Related to Trastuzumab Resistance in Gastric Cancer Cells

“…As reported previously, BCL-2 was a famous oncogene that suppressed apoptosis in human cancer cells [ 15 , 16 ]. BCL-2 was oncogenic in gastric cancer [ 15 , 17 ]. Moreover, BCL-2 was associated with methotrexate resistance in gastric cancer cells [ 18 ].…”