TCP1 promotes the progression of malignant tumors by stabilizing c-Myc through the AKT/GSK-3β and ERK signaling pathways

Abstract

TCP1, one of the subunits of molecular chaperone containing tailless complex polypeptide 1 (CCT) (CCT1), maybe play an essential role in cell proliferation and tumorigenesis. However, the biological functions and the underlying mechanisms of TCP1 in tumors are not fully understood. Here, we found that TCP1 levels increased with successive generations of xenografted tumors and were associated with the tumorigenicity of HL-60 cells. TCP1 expression was significantly higher in de novo and recurrent leukemia clinical samples and in various solid tumor tissues than in their related normal tissues. High expression of TCP1 was significantly associated with poor outcomes in patients with pancreatic ductal adenocarcinoma (PDAC) and HCC. Functional assays and mechanistic studies revealed that TCP1 suppression not only decreased the proliferation and invasion of cancer cells in vitro but also inhibited tumor growth and metastatic spread in vivo. Ubiquitination assays and mechanistic studies revealed that TCP1 regulated the stability of c-Myc through the AKT/GSK-3β and ERK signaling pathways. Moreover, TCP1 knockin (TCP1-KI) mice, which generated by CRISPR/Cas9-mediated genome engineering, dramatically facilitated the occurrence of DEN-induced HCC. Our results demonstrate a novel mechanism of TCP1 regulation in multiple malignant tumors, and targeting TCP1 may provide new therapeutic strategies for the cancer treatment.

Sparse Friendly Distillation Using Feature Decoupling

“…In recent years, deep neural networks have achieved remarkable success in various computer vision tasks. However, the high computational cost and memory requirements of large neural networks have become a major obstacle to their deployment on resource-constrained devices [2,5,10,25]. Model sparsity is a promising approach to address this issue by reducing the number of parameters in the deep neural network.…”

Deltoid ligament (DL) repair produced better results than DL nonrepair for the treatment for rotational ankle instability

“…To date, the appropriate treatment for DL injury is still controversial in ankle sprains [3,13,16,30]. DL injury in cases of ankle fracture can be treated via conservative management with good results, and no chronic medial instability was observed [6,17,27,28]. On the other hand, it has been shown that concomitant DL repair enhanced ankle stability in an ankle with both syndesmotic and DL disruptions [24].…”