<p>TMEFF2 inhibits pancreatic cancer cells proliferation, migration, and invasion by suppressing phosphorylation of the MAPK signaling pathway</p>

Abstract

PurposeThis paper studied the effect of TMEFF2 expression on pancreatic cancer and its mechanism.MethodsA total of 72 pancreatic cancer patients were enrolled. AsPC1 and Panc1 cells were transfected. SB203580 was used to treat AsPC1 cells. CCK8 assay, colony formation analysis, Transwell experiment and Tunel test were performed. In vivo studies in nude mice were conducted. Immunohistochemistry, qRT-PCR and Western blot were used to detect genes expression.ResultsTMEFF2 was downregulated in pancreatic cancer tissues and cells (P<0.001). Low TMEFF2 expression was associated with larger tumor size and advanced stage and poor differentiation (P<0.01). Compared with the NC group, AsPC1 and Panc1 cells of the TMEFF2 group exhibited much lower OD450 values, colony number, tumor volume and weight, migration and invasion cell numbers, obviously higher E-cadherin protein expression, lower Snail, Vimentin, MMP-2 and MMP-9 proteins expression, lower phosphorylation level of MAPK signaling pathway, and more apoptotic cells. AsPC1 cells of the SB203580 group showed much lower OD450 value when compared with the siTMEFF2 group. Significantly decreased colony number, migration and invasion number, higher E-cadherin protein expression and lower Snail, Vimentin, MMP-2 and MMP-9 proteins expression were found in AsPC1 cells of the siTMEFF2+ SB203580 group when compared with the siTMEFF2+ DMSO group.ConclusionTMEFF2 inhibits pancreatic cancer cells proliferation, migration, and invasion by suppressing the phosphorylation of the MAPK signaling pathway.

The design and development of covalent protein-protein interaction inhibitors for cancer treatment

“…For example, S100A13 overexpression contributed to tumor metastasis and poor survival in patients with early-stage non-small cell lung cancer [16]. Low TMEFF2 expression was associated with larger tumor size and advanced stage and poor differentiation in pancreatic cancer cells [17]. It was reported that more than 50% of cancer patients have p53 mutations, which may cause cancer therapy resistance, and the underlying mechanism is poorly understood [18].…”

Integrated Analysis of tRNA-Derived Small RNAs in Proliferative Human Aortic Smooth Muscle Cells

“…Thus, AS-tDR-000067 may inhibit the process of apoptosis by targeting PYCARD. As the downstream target genes of AS-tDR-009512, TPM1 [110], TMEFF2 [111], and PTPRJ [112,113] are involved in cell proliferation and metastasis. It has been reported that TPM1 is involved in the inhibition of VSMC proliferation and metastasis [110].…”

TMEFF2: A Transmembrane Proteoglycan with Multifaceted Actions in Cancer and Disease

“…Using RT-PCR, Zhao et al [ 15 ] observed low levels of tomoregulin mRNA in kidney tissue and minimal levels in testis. Han et al [ 48 ] observed the expression of TMEFF2 mRNA and protein in pancreatic cancer and normal pancreatic tissue. Intriguingly, Glynne-Jones et al [ 12 ] used northern tissue arrays and reported TENB2 mRNA present only in prostate tissue and brain (adult and foetal) except in the pituitary gland.…”

“…Yonezawa et al [ 11 ] reported weak expression in stomach fibroblasts, RD human embryonal rhabdomyosarcoma cells and PC12 rat pheochromocytoma cells in addition to the A172 glioblastoma and CHO-K1 cells. Han et al [ 48 ] reported the expression of both the protein and mRNA of TMEFF2 in five pancreatic cancer cell lines—SW1990, Bxpc3, CFPAC1, Panc1 and AsPC1—and in the normal pancreatic ductal epithelial cells HPDE6-C7. Labeur et al [ 6 ] used AtT20 pituitary corticotrope tumour cells for TMEFF2 knockdown studies.…”

“…On the other hand, when compared to adjacent normal tissue, TMEFF2 mRNA was downregulated in pancreatic cancer (72 patients) [ 48 ], and an inverse correlation was observed between TEMFF2 protein in pancreatic cancer tissue and the clinical stage of the disease. The study also reported that TMEFF2 overexpression in AsPC1 and Panc1 pancreatic cancer cells (i) impairs cell proliferation both in vitro and in vivo (xenograft), (ii) decreases their invasion and migration capacities, and (iii) downregulates EMT signature proteins.…”