Microsatellite instability (MSI), which occurs in 15% of colorectal cancer, has been shown to have a lower incidence of metastasis and better patient survival rates compared with microsatellite stable colorectal cancer. However, a mechanistic understanding of the basis for this difference is very limited. Here, we show that restoration of TGFβ signaling by re-expression of TGFβ receptor II in MSI colon cancer cells increased PI3K/AKT activation, conferred resistance to growth factor deprivation stress-induced apoptosis, and promoted cell motility in vitro. Treatment with a potent PI3K inhibitor (LY294002) blocked the prosurvival and promotility effects of TGFβ, indicating that TGFβ-mediated promotion of cell survival and motility is dependent upon activation of the PI3K/AKT pathway. Analysis of apoptotic effectors that are affected by TGFβ signaling indicated that Bim is an effector of TGFβ-mediated survival. In addition, TGFβ-induced down-regulation of E-cadherin contributed to the prosurvival effect of TGFβ, and restoration of TGFβ signaling in MSI colon cancer cells increased liver metastasis in an orthotopic model in vivo. Taken together, our results demonstrate that restoration of TGFβ signaling promotes cell survival, motility, and metastatic progression in MSI colon cancer cells and indicate that TGFβ receptor II mutations contribute to the favorable outcomes in colon cancer patients with MSI.
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http://dx.doi.org/10.1074/jbc.M111.221697 | DOI Listing |
tumour specific surgery in colon cancer is gaining popularity among colorectal surgeons. Many advocate adapting surgical technique based on preoperative CT staging as not all patients require complete mesocolic excision (CME) and D3 lymphadenectomy. We aimed to assess the sensitivity and specificity of preoperative CT scans in nodal staging and analyse whether inadequate CT staging could have influenced local recurrences.
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November 2024
The First Clinical Medical College, Jinan University, Guangzhou, China.
Objective: Colorectal cancer is severely challenging because of the insufficient understanding of the mechanism underlying its resistance to clinical chemotherapy. The purpose of our study is to investigate the role of the LIM protein Ajuba (JUB) in the chemoresistance of colon cancer and its potential effect on clinical treatment.
Material And Methods: The protein levels of JUB in colon cancer tissues were evaluated using Western blot analysis and immunohistochemistry assays.
Cureus
December 2024
General Surgery, Aneurin Bevan University Health Board, Newport, GBR.
Aim: To assess recent colonoscopies and CT scans in conjunction with the feacal immunochemical test (FIT) for possibly downgrading urgent suspected cancer (USC) referrals.
Methods: A retrospective single-centre study was conducted, including all USC referrals for colonoscopy in 2022, excluding anal cancers. The CT and colonoscopy findings for a two-year period prior to the referral, along with the FIT result (if done), were noted.
BMC Public Health
December 2024
Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah, United Arab Emirates.
Background: Cancer is one of the leading causes of death in children and adolescents, with a significant concentration in low and middle-income countries. Previous research has identified disparities in cancer incidence and mortality based on a country's level of development. The Middle East and North Africa (MENA) region comprises of countries with heterogeneous income and development levels.
View Article and Find Full Text PDFBMC Prim Care
December 2024
Department of Internal Medicine, Division of Endocrinology and Metabolism, Cerrahpasa Medical Faculty, Istanbul University Cerrahpasa, Istanbul, Turkey.
Background: Acromegaly is a disease with high morbidity and mortality rates. The role of primary care physicians is very important in the early diagnosis of acromegaly. The present study aims to determine the knowledge and attitudes of primary care physicians about acromegaly in different countries worldwide.
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