MARK1 suppress malignant progression of hepatocellular carcinoma and improves sorafenib resistance through negatively regulating POTEE.

Purpose: This study aimed to investigate the role of microtubule-affinity regulatory protein kinase 1 (MARK1) in hepatocellular carcinoma (HCC) progression, its association with sorafenib sensitivity, and the interplay between MARK1 and POTE Ankyrin domain family member E(POTEE) in HCC cells.

Methods: Quantitative real-time polymerase chain reaction analysis was used to assess MARK1 and POTEE expression in 60 pairs of HCC tissues and cell lines. The correlation between MARK1 levels, clinicopathological features, and patient prognosis was analyzed.

Linear-Array Endoscopic Ultrasound and Narrow-Band Imaging Measure the Invasion Depth of Nonpedunculated Rectal Lesions With Comparable Accuracy Based on a Randomized Controlled Trial.

Introduction: Linear-array endoscopic ultrasound (EUS) and narrow-band imaging (NBI) are both used to estimate the invasion depth of nonpedunculated rectal lesions (NPRLs). However, it is unclear which procedure is more accurate. This randomized controlled trial aimed to compare the diagnostic accuracy of linear EUS and NBI for estimating the invasion depth of NPRLs.

Linear-array EUS improves the accuracy of predicting deep submucosal invasion in non-pedunculated rectal polyps compared with radial EUS: a prospective observational study.

Background: Radial endoscopic ultrasound (EUS) is typically used to estimate the depth of rectal polyp invasion, however, there are no data on linear EUS in this setting and its relative accuracy compared to radial EUS.

Methods: In this prospective cohort study, 89 patients with non-pedunculated rectal polyp who underwent linear EUS or radial EUS were prospectively enrolled. The invasion depth was measured for each polyp and categorized as mucosal to shallow submucosal(SM) or deep submucosal(SM) invasion.

N-glycosylation-defective splice variants of neuropilin-1 promote metastasis by activating endosomal signals.

Neuropilin-1 (NRP1) is an essential transmembrane receptor with a variety of cellular functions. Here, we identify two human NRP1 splice variants resulting from the skipping of exon 4 and 5, respectively, in colorectal cancer (CRC). Both NRP1 variants exhibit increased endocytosis/recycling activity and decreased levels of degradation, leading to accumulation on endosomes.

Snail determines the therapeutic response to mTOR kinase inhibitors by transcriptional repression of 4E-BP1.

Loss of 4E-BP1 expression has been linked to cancer progression and resistance to mTOR inhibitors, but the mechanism underlying 4E-BP1 downregulation in tumors remains unclear. Here we identify Snail as a strong transcriptional repressor of 4E-BP1. We find that 4E-BP1 expression inversely correlates with Snail level in cancer cell lines and clinical specimens.

AKT inhibition overcomes rapamycin resistance by enhancing the repressive function of PRAS40 on mTORC1/4E-BP1 axis.

The mTORC1 inhibitors, rapamycin and its analogs, are known to show only modest antitumor activity in clinic, but the underlying mechanisms remain largely elusive. Here, we found that activated AKT signaling is associated with rapamycin resistance in breast and colon cancers by sustained phosphorylation of the translational repressor 4E-BP1. Treatment of tumor cells with rapamycin or the AKT inhibitor MK2206 showed a limited activity in inhibiting 4E-BP1 phosphorylation, cap-dependent translation, cell growth and motility.