TY  - JOUR
AB  - Obesity is an established risk factor for several human cancers. Given the association between excess body weight and cancer, the increasing rates of obesity worldwide are worrisome. A variety of obesity-related factors has been implicated in cancer initiation, progression, and response to therapy. These factors include circulating nutritional factors, hormones, and cytokines, causing hyperinsulinemia, inflammation, and adipose tissue dysfunction. The impact of these conditions on cancer development and progression has been the focus of extensive literature. In this review, we concentrate on processes that can link obesity and cancer, and which provide a novel perspective: extracellular matrix remodeling, angiogenesis, and adrenergic signaling. We describe molecular mechanisms involved in these processes, which represent putative targets for intervention. Liver, pancreas, and breast cancers were chosen as exemplary disease models. In view of the expanding epidemic of obesity, a better understanding of the tumorigenic process in obese individuals might lead to more effective treatments and preventive measures.
AU  - Pellegata, N.S.
AU  - Berriel Diaz, M.
AU  - Rohm, M.
AU  - Herzig, S.
C1  - 66163
C2  - 53101
SP  - 517–547
TI  - Obesity and cancer-extracellular matrix, angiogenesis, and adrenergic signaling as unusual suspects linking the two diseases.
JO  - Cancer Metastasis Rev.
VL  - 41
PY  - 2022
SN  - 0167-7659
ER  - 

TY  - JOUR
AB  - It is well established that cancer cells acquire energy via the Warburg effect and oxidative phosphorylation. Citrate is considered to play a crucial role in cancer metabolism by virtue of its production in the reverse Krebs cycle from glutamine. Here, we review the evidence that extracellular citrate is one of the key metabolites of the metabolic pathways present in cancer cells. We review the different mechanisms by which pathways involved in keeping redox balance respond to the need of intracellular citrate synthesis under different extracellular metabolic conditions. In this context, we further discuss the hypothesis that extracellular citrate plays a role in switching between oxidative phosphorylation and the Warburg effect while citrate uptake enhances metastatic activities and therapy resistance. We also present the possibility that organs rich in citrate such as the liver, brain and bones might form a perfect niche for the secondary tumour growth and improve survival of colonising cancer cells. Consistently, metabolic support provided by cancer-associated and senescent cells is also discussed. Finally, we highlight evidence on the role of citrate on immune cells and its potential to modulate the biological functions of pro- and anti-tumour immune cells in the tumour microenvironment. Collectively, we review intriguing evidence supporting the potential role of extracellular citrate in the regulation of the overall cancer metabolism and metastatic activity.
AU  - Parkinson, E.K.*
AU  - Adamski, J.
AU  - Zahn, G.*
AU  - Gaumann, A.*
AU  - Flores-Borja, F.*
AU  - Ziegler, C.*
AU  - Mycielska, M.E.*
C1  - 63894
C2  - 51640
CY  - Van Godewijckstraat 30, 3311 Gz Dordrecht, Netherlands
TI  - Extracellular citrate and metabolic adaptations of cancer cells.
JO  - Cancer Metastasis Rev.
PB  - Springer
PY  - 2021
SN  - 0167-7659
ER  - 

TY  - JOUR
AB  - EpCAM (epithelial cell adhesion molecule) was discovered four decades ago as a tumor antigen on colorectal carcinomas. Owing to its frequent and high expression on carcinomas and their metastases, EpCAM serves as a prognostic marker, a therapeutic target, and an anchor molecule on circulating and disseminated tumor cells (CTCs/DTCs), which are considered the major source for metastatic cancer cells. Today, EpCAM is reckoned as a multi-functional transmembrane protein involved in the regulation of cell adhesion, proliferation, migration, stemness, and epithelial-to-mesenchymal transition (EMT) of carcinoma cells. To fulfill these functions, EpCAM is instrumental in intra- and intercellular signaling as a full-length molecule and following regulated intramembrane proteolysis, generating functionally active extra- and intracellular fragments. Intact EpCAM and its proteolytic fragments interact with claudins, CD44, E-cadherin, epidermal growth factor receptor (EGFR), and intracellular signaling components of the WNT and Ras/Raf pathways, respectively. This plethora of functions contributes to shaping intratumor heterogeneity and partial EMT, which are major determinants of the clinical outcome of carcinoma patients. EpCAM represents a marker for the epithelial status of primary and systemic tumor cells and emerges as a measure for the metastatic capacity of CTCs. Consequentially, EpCAM has reclaimed potential as a prognostic marker and target on primary and systemic tumor cells.
AU  - Gires, O.
AU  - Pan, M.*
AU  - Schinke, H.*
AU  - Canis, M.*
AU  - Baeuerle, P.A.*
C1  - 59321
C2  - 48737
CY  - Van Godewijckstraat 30, 3311 Gz Dordrecht, Netherlands
SP  - 969–987
TI  - Expression and function of epithelial cell adhesion molecule EpCAM: Where are we after 40 years?
JO  - Cancer Metastasis Rev.
VL  - 39
PB  - Springer
PY  - 2020
SN  - 0167-7659
ER  -