ASPP1 deficiency promotes epithelial-mesenchymal transition, invasion and metastasis in colorectal cancer

Abstract

The apoptosis-stimulating protein of p53 (ASPP) family of proteins can regulate apoptosis by interacting with the p53 family and have been identified to play an important role in cancer progression. Previously, we have demonstrated that ASPP2 downregulation can promote invasion and migration by controlling β-catenin-dependent regulation of ZEB1, however, the role of ASPP1 in colorectal cancer (CRC) remains unclear. We analyzed data from The Cancer Genome Atlas (TCGA) and coupled this to in vitro experiments in CRC cell lines as well as to experimental pulmonary metastasis in vivo. Tissue microarrays of CRC patients with information of clinical-pathological parameters were also used to investigate the expression and function of ASPP1 in CRC. Here, we report that loss of ASPP1 is capable of enhancing migration and invasion in CRC, both in vivo and in vitro. We demonstrate that depletion of ASPP1 could activate expression of Snail2 via the NF-κB pathway and in turn, induce EMT; and this process is further exacerbated in RAS-mutated CRC. ASPP1 could be a prognostic factor in CRC, and the use of NF-κB inhibitors may provide new strategies for therapy against metastasis in ASPP1-depleted CRC patients.

Non‐coding RNA‐associated competitive endogenous RNA regulatory networks: Novel diagnostic and therapeutic opportunities for hepatocellular carcinoma

“… 97 , 98 SOX9 has been reported to be implicated in regulating various cellular processes including proliferation, apoptosis, migration, invasion, chemoresistance, autophagy, angiogenesis, immune escape and metastasis by controlling the transcription of a multitude of genes. 99 , 100 Multiple lines of evidence support the suggestion that SOX9 is involved in the development of diverse types of malignancies such as bladder, brain, colon, cervical, gastric, endometrial, liver, and head and neck cancers. 101 , 102 , 103 , 104 , 105 , 106 , 107 , 108 , 109 It has been revealed that SOX9 is up‐regulated in HCC and contributes to the proliferation, migration and invasion of HCC cells.…”

WDHD1 is essential for the survival of PTEN-inactive triple-negative breast cancer

“…After incubation with secondary goat anti-rabbit immunoglobulin conjugated to peroxidaselabelled dextran polymer (SV0002; Boster) at 37°C for 1 h, visualisation, counterstaining with haematoxylin and mounting were performed. Semi-quantitative evaluations of protein expression were scored on the basis of the intensity and the percentage of WDHD1-positive tumour cells as previously described [59][60][61][62] .…”

The type-1 ribosome-inactivating protein OsRIP1 triggers caspase-independent apoptotic-like death in HeLa cells

“…The first protein ASPP1 is a common activator of the p53 family member, and specifically enhances the apoptotic function of p53/p63/p73, through up-regulation of proapoptotic target genes such as PUMA, Bax, FAS and PIG3 (Liu et al, 2020). An OsRIP1-induced increase of RNA levels for PUMA was already observed after 6 h, but was higher after 12 h. PUMA is known as an essential modulator of the p53-dependent and -independent apoptotic signaling pathway for many years (Yu and Zhang, 2008).…”