Nucleostemin interacts with SMAD3 promoting tumor metastasis.

SMAD3 plays a crucial role in TGF-β, regulating various normal developmental mechanisms and disease pathogenesis. Here, we report that SMAD3 directly interacts with Nucleostemin (NS), leading to nuclear translocation and affecting SMAD3 activity after TGF-β1 stimulation. Moreover, NS acts as a competitor, preventing PPM1A from recognizing and dephosphorylating SMAD3.

CLK3 promotes tumor proliferation by activating MYC signaling.

Colorectal cancer (CRC) ranks among the leading causes of cancer-related mortality worldwide, posing a significant public health challenge. Despite advancements in treatment strategies, prognosis for advanced CRC remains poor. Here, we investigate the role of CLK3 and its interaction with the c-Myc signaling pathway in CRC progression.

PRMT5 methylating SMAD4 activates TGF-β signaling and promotes colorectal cancer metastasis.

Perturbations in transforming growth factor-β (TGF-β) signaling can lead to a plethora of diseases, including cancer. Mutations and posttranslational modifications (PTMs) of the partner of SMAD complexes contribute to the dysregulation of TGF-β signaling. Here, we reported a PTM of SMAD4, R361 methylation, that was critical for SMAD complexes formation and TGF-β signaling activation.

TRIB3 Interacts with STAT3 to Promote Cancer Angiogenesis.

Objective: Vascular endothelial growth factor A (VEGFA) is a key regulator of angiogenesis, which is a hallmark of cancer that promotes cancer growth and metastasis. It is of great significance to find new intervention targets and related regulatory mechanisms of VEGFA related angiogenesis for the treatment of tumors. This study focuses on the role of tribbles pseudokinase 3 (TRIB3)/signal transducer and activator of transcription 3 (STAT3)/VEGFA signaling axis in colon cancer angiogenesis.

EZH2-triggered methylation of SMAD3 promotes its activation and tumor metastasis.

SMAD3 plays a central role in cancer metastasis, and its hyperactivation is linked to poor cancer outcomes. Thus, it is critical to understand the upstream signaling pathways that govern SMAD3 activation. Here, we report that SMAD3 underwent methylation at K53 and K333 (K53/K333) by EZH2, a process crucial for cell membrane recruitment, phosphorylation, and activation of SMAD3 upon TGFB1 stimulation.

PIK3R3 inhibits cell senescence through p53/p21 signaling.

Cellular senescence is a stress response of human cells that removes potentially harmful cells by initiating cell cycle arrest. Inducing senescence of tumor cells may be an effective tumor-inhibiting strategy. In this study we found that PIK3R3 could inhibit the cell senescence of colorectal cancer cells and promote cell proliferation through the p53/p21 signal pathway.

SIX4 promotes metastasis through STAT3 activation in breast cancer.

Sine oculis homeobox homolog 4 (SIX4), a member of the SIX family, play important role in the development and construction of vertebrate tissues and organs. There is very little known about the function of SIX4 in cancer cells. Herein, we investigated whether SIX4 promote cancer metastasis in addition to its direct role in breast cancer cells.

SIX4 activates Akt and promotes tumor angiogenesis.

Angiogenesis plays important roles in solid tumors progression. Growth factors such as vascular endothelial growth factors (VEGFs) can induce angiogenesis and hypoxia promotes the expression of VEGFs through activating hypoxia-inducible factor 1 (HIF-1α). However, the regulation of HIF-1α still not been fully understood.

Inhibition of SIRT2 limits tumour angiogenesis via inactivation of the STAT3/VEGFA signalling pathway.

Mounting evidence has demonstrated that angiogenesis plays an important role in tumour progression. However, the key regulators in tumour angiogenesis remain unclear. Recently, emerging reports have indicated that SIRT2 plays critical roles in proliferation, metastasis and tumourigenesis in diverse tumours.

TRIB2 functions as novel oncogene in colorectal cancer by blocking cellular senescence through AP4/p21 signaling.

Background: Cellular senescence is a state of irreversible cell growth arrest and senescence cells permanently lose proliferation potential. Induction of cellular senescence might be a novel therapy for cancer cells. TRIB2 has been reported to participate in regulating proliferation and drug resistance of various cancer cells.

The combination therapy of high-intensity focused ultrasound with radiotherapy in locally advanced pancreatic carcinoma.

Background: The aim of the present study is to evaluate the effectiveness of the combined application of high-intensity focused ultrasound (HIFU) and radiotherapy in the treatment of locally advanced pancreatic carcinoma (LAPC).

Methods: A total number of sixteen patients with LAPC started treatment beginning with HIFU and radiotherapy 1 week after the HIFU treatment. Evaluation of the effectiveness of treatment was performed using main clinical symptoms, serum levels of CA-19-9, Response Evaluation Criteria in Solid Tumors (RECIST) guidelines, and the Kaplan-Meier method for estimating median overall survival (OS).