Deubiquitylation of Rab35 by USP32 promotes the transmission of imatinib resistance by enhancing exosome secretion in gastrointestinal stromal tumours.

Imatinib is a tyrosine kinase inhibitor that is widely used to combat gastrointestinal stromal tumours (GISTs). However, secondary resistance to imatinib is an important challenge in GIST treatment. Recent studies have demonstrated that cancer-derived nanosized exosomes play a key role in intercellular communication, but little is known about the roles of exosomes in imatinib-resistant GISTs.

N-methyladenosine-modified USP13 induces pro-survival autophagy and imatinib resistance via regulating the stabilization of autophagy-related protein 5 in gastrointestinal stromal tumors.

Secondary resistance to imatinib (IM) represents a major challenge for therapy of gastrointestinal stromal tumors (GISTs). Aberrations in oncogenic pathways, including autophagy, correlate with IM resistance. Regulation of autophagy-related protein 5 (ATG5) by the ubiquitin-proteasome system is critical for autophagic activity, although the molecular mechanisms that underpin reversible deubiquitination of ATG5 have not been deciphered fully.

METTL3-Mediated ADAMTS9 Suppression Facilitates Angiogenesis and Carcinogenesis in Gastric Cancer.

The role of methyltransferase-like 3 (METTL3), which participates in catalyzing N-methyladenosine (m6A) RNA modification, in gastric cancer (GC) is unclear. Here, we found that METTL3 was overexpressed in human GC. Functionally, we verified that METTL3 promoted tumor cell proliferation and angiogenesis through a series of phenotypic experiments.

Substrate rigidity dictates colorectal tumorigenic cell stemness and metastasis via CRAD-dependent mechanotransduction.

Tumor physical microenvironment contributes greatly to the response of tumor cells. However, the mechanism of how extracellular substrate rigidity remodels colorectal cancer (CRC) cell fate and affects CRC progression remains elusive. Here, we show that F-actin regulator KIAA1211, also known as Capping protein inhibiting regulator of actin dynamics (CRAD), negatively correlates with CRC progression, stemness, and metastasis.

N-methyladenosine modification regulates imatinib resistance of gastrointestinal stromal tumor by enhancing the expression of multidrug transporter MRP1.

N-methyladenosine (mA) is a frequently occurring mRNA modification, which regulates mRNA stability, splicing, and translation. However, its role in drug resistance of gastrointestinal stromal tumor (GIST) is not known. Here, we report that mA modification levels are elevated in imatinib-resistant GIST cells and tissues, and that methyltransferase METTL3 is one of the main protein responsible for this aberrant modification.

HIF-1α regulates cellular metabolism, and Imatinib resistance by targeting phosphogluconate dehydrogenase in gastrointestinal stromal tumors.

The pentose phosphate pathway (PPP) plays a critical role in maintaining cellular redox homeostasis in tumor cells and macromolecule biosynthesis. Upregulation of the PPP has been shown in several types of tumor. However, how the PPP is regulated to confer selective growth advantages on drug resistant tumor cells is not well understood.

HMGA1 Regulates the Stem Cell-Like Properties of Circulating Tumor Cells from GIST Patients via Wnt/β-Catenin Pathway.

Background: Gastrointestinal stromal tumor (GIST) is the most common sarcoma of the digestive system. Circulating tumor cells (CTCs) have been proven to be critical in the recurrence and metastasis of diseases; however, the characteristics of CTCs of GIST are still unclear.

Methods: We sorted out and verified the validity of CTCs from peripheral blood of gastrointestinal stromal tumor (GIST) patients with or without heterochronous liver metastasis using flow cytometry (FCM).

Circulating tumor cells in whole process management of gastrointestinal stromal tumor in a real-life setting.

Background/aim: Liquid biopsy is changing the diagnosis and treatment strategies of various neoplasms. However, the circulating tumor cells (CTCs) of gastrointestinal stromal tumor (GIST) patients with different disease process are not clear. To better understand the dynamic change of CTCs in GIST patients, we conducted a real-life setting study.