MIST1 regulates SNAI1 and acts through the PTEN/AKT signaling axis to promote anoikis resistance in human melanoma cells

Abstract

Cutaneous malignant melanoma (CMM) is one of the most dangerous types of skin cancer. The prognosis of CMM patients with ulcers, regional lymph node metastasis or organ metastasis is poor. In this process, resistance to anoikis is a critical step in tumor cell metastasis. Tumor cells survive in the vascular and lymphatic system through the escape of anoikis to finally form clones in the distal tissue. The present study revealed that muscle intestine and stomach expression 1 (MIST1), a secreting cell-restricted transcription factor, was overexpressed in melanoma cells. At the same time, the expression of SNAI1 was also high. High expression of MIST1 and SNAI1 all contributed to melanoma cells bypassing anoikis. By changing the expression of MIST1, SNAI1 was indicated to be a downstream gene of MIST1. Chromatin immunoprecipitation and luciferase reporter gene technology revealed that MIST1 promoted the expression of SNAI1 by directly binding to its promoter region. Furthermore, inhibition of the phosphorylation/activity of Akt by LY294002 and knockdown of phosphatase and tensin homologue (PTEN) with simultaneous upregulation or knockdown of MIST1 revealed that SNAI1 improved the phosphorylation of Akt by inhibiting the expression of PTEN. These results suggested that MIST1 hijacked the PTEN/AKT signaling pathway through directly regulating SNAI1 and affected the anoikis resistance capacity of melanoma cells.

DDX56 transcriptionally activates MIST1 to facilitate tumorigenesis of HCC through PTEN-AKT signaling

“…MIST1 reportedly hijacks the PTEN-AKT signaling pathway to promote anoikic resistance in skin cancer 15 . Therefore, we investigated whether MIST1 contributes to HCC development by regulating the PTEN-AKT pathway.…”

“…Muscle intestine stomach expression 1 (MIST1), also known as BHLHA15, belongs to the basic helix-loop-helix (bHLH) superfamily, which plays a dual role in cancer development. MIST1 is regarded as a tumor promoter in multiple cancers, including cervical cancer 12 , colon cancer 13 , acinic cell carcinoma 14 , and cutaneous malignant melanoma 15 . However, previous studies have shown that upregulation of MIST1 reverses epithelial-mesenchymal transition (EMT) and attenuates the tumorigenicity of pancreatic cancer and gastric cancer 16 , 17 .…”

Long Non-Coding RNA MAPK8IP1P2 Inhibits Lymphatic Metastasis of Thyroid Cancer by Activating Hippo Signaling via Sponging miR-146b-3p

“…Several lines of evidence have reported the pivotal role of anoikis resistance in lymphatic metastasis of cancer (10,11), even in lymphatic metastasis of thyroid cancer (18)(19)(20). Furthermore, anoikis resistance was reported to be significantly correlated with positive lymph node metastasis in various cancers (12)(13)(14)(15)(16)(17). In this scenario, multiple signaling pathways have been demonstrate to promote anoikis resistance, including TGF-b, PI3K/AKT, and Hippo signaling, where the role of Hippo signaling in inducing anoikis resistance gains more attention (9,50,51).…”

“…Recently, the critical role of anoikis resistance in lymphatic metastasis of cancer seizes great attention ( 10 , 11 ). In several cancer scenario, anoikis resistance correlated significantly with positive lymph node metastasis status, including esophageal carcinoma ( 12 , 13 ), melanoma ( 14 ), tongue cancer ( 15 ), breast cancer ( 16 ), and colorectal cancer ( 17 ). Importantly, development of anoikis resistance has been reported to significantly contribute to lymphatic metastasis of thyroid cancer ( 18 – 20 ).…”

Mist1 Inhibits Epithelial-Mesenchymal Transition in Gastric Adenocarcinoma via Downregulating the Wnt/β-catenin Pathway

“…The expression of Mist1 in human gastric development and maturation has been described in recent years, and Mist1 has been suggested to regulate the maturation of exocrine granules via the RAB26/RAB3D complex and act a chief cell marker of gastric mucosa regeneration [17,20,27]. Recently, an increasing number of studies have addressed the role of Mist1 in the carcinogenesis and development of pancreatic cancer, melanoma and salivary gland acinic cell carcinoma [28][29][30]. Here, in our study, we found that Mist1 was downregulated in gastric carcinogenesis.…”