Establishment and drug resistance characterization of paired organoids using human primary colorectal cancer and matched tumor deposit specimens.

Tumor deposits (TDs) represent a specific form tumor metastasis observed in colorectal cancer (CRC). The lack of successfully established cell lines for TDs, as well as the molecular mechanisms by which TDs occur remain largely unknown. Here, we established paired CRC organoids, including a human primary cancer organoid and its TD organoid, from a 46-year-old male patient with CRC.

Nuclear Softness Promotes the Metastatic Potential of Large-Nucleated Colorectal Cancer Cells via the ErbB4-Akt1-Lamin A/C Signaling Pathway.

Abnormal nuclear enlargement is a diagnostic and physical hallmark of malignant tumors. Large nuclei are positively associated with an increased risk of developing metastasis; however, a large nucleus is inevitably more resistant to cell migration due to its size. The present study demonstrated that the nuclear size of primary colorectal cancer (CRC) cells at an advanced stage was larger than cells at an early stage.

DAB2IP suppresses invadopodia formation through destabilizing ALK by interacting with USP10 in breast cancer.

Invadopodia, being actin-rich membrane protrusions, play a vital role in tumor cell invasion and metastasis. Our previous studies have revealed some functions of the DOC-2/DAB2 interacting protein (DAB2IP) as a tumor suppressor. Nevertheless, the specific role and mechanism of DAB2IP in invadopodia formation remain unclear.

Lactate promotes metastasis of normoxic colorectal cancer stem cells through PGC-1α-mediated oxidative phosphorylation.

Uneven oxygen supply in solid tumors leads to hypoxic and normoxic regions. Hypoxic cells exhibit increased secretion of lactate, which creates an acidic tumor microenvironment (TME). This acidic TME is positively associated with tumor metastasis.

YAP1 induces invadopodia formation by transcriptionally activating TIAM1 through enhancer in breast cancer.

Yes-associated protein 1 (YAP1), a central component of the Hippo pathway, plays an important role in tumor metastasis; however, the underlying mechanism remains to be elucidated. Invadopodia are actin-rich protrusions containing multiple proteases and have been widely reported to promote cell invasiveness by degrading the extracellular matrix. In the present study, we report that YAP1 induces invadopodia formation and promotes tumor metastasis in breast cancer cells.

Aptamer-protamine-siRNA nanoparticles in targeted therapy of ErbB3 positive breast cancer cells.

Background: RNAi-based technology has achieved good results in both in vitro and in vivo applications, and it is expected to become a good genetic treatment for some diseases, especially neoplastic diseases. But there are still many obstacles in the in vivo application, the most important thing is the lack of an efficient and safe carrier.

Methods: In this study, we designed and constructed a new siRNA delivery, which was named as aptamer-protamine-siRNA nanoparticle (APR).

Hypoxic colorectal cancer cells promote metastasis of normoxic cancer cells depending on IL-8/p65 signaling pathway.

Tumor heterogeneity is an important feature of malignant tumors, and cell subpopulations may positively interact to facilitate tumor progression. Studies have shown that hypoxic cancer cells possess enhanced metastatic capacity. However, it is still unclear whether hypoxic cancer cells may promote the metastasis of normoxic cells, which have greater access to the blood circulation.

Sphere‑forming assay vs. organoid culture: Determining long‑term stemness and the chemoresistant capacity of primary colorectal cancer cells.

Three‑dimensional (3D) cultures are indispensable for capturing tumor heterogeneity in colorectal cancer (CRC) in vitro. Although 3D cultures (such as sphere‑forming assay and organoid culture) can partially preserve the morphological and molecular characteristics of primary CRC, whether these 3D cultures maintain the long‑term stemness of cancer stem cells (CSCs) remains largely unknown. In the present study, spheres and organoids were generated side by side using individual primary CRC specimens, then respectively processed as serial passages.

Hippo component YAP promotes focal adhesion and tumour aggressiveness via transcriptionally activating THBS1/FAK signalling in breast cancer.

Background: Focal adhesion plays an essential role in tumour invasiveness and metastasis. Hippo component YAP has been widely reported to be involved in many aspects of tumour biology. However, its role in focal adhesion regulation in breast cancer remains unexplored.

Small-sized colorectal cancer cells harbor metastatic tumor-initiating cells.

Colorectal cancer (CRC) is heterogeneous and contains different-sized cells. Recent studies have shown that tumor-initiating cells (TICs) are involved in cancer initiation, recurrence and metastasis. However, connections between cancer cell size and stem-like properties are largely unknown.

The CEA-/lo colorectal cancer cell population harbors cancer stem cells and metastatic cells.

Serum carcinoembryonic antigen (CEA) is the most commonly used tumor marker in a variety of cancers including colorectal cancer (CRC) for tumor diagnosis and monitoring. Recent studies have shown that colonic crypt cells expressing little or no CEA may enrich for stem cells. Numerous studies have clearly shown that there exist CRC patients with normal serum CEA levels during tumor progression or even tumor relapse, although CEA itself is considered to promote metastasis and block cell differentiation.

KDM4B plays an important role in mitochondrial apoptosis by upregulating HAX1 expression in colorectal cancer.

Histone methyltransferases and demethylases regulate transcription by altering the epigenetic marks on histones in tumorigenesis. Members of the histone lysine(K)-specific demethylase 4 (KDM4) family are dysregulated in several types of cancer. Here, we report a novel role for KDM4B in mitochondrial apoptosis.

Absence of DAB2IP promotes cancer stem cell like signatures and indicates poor survival outcome in colorectal cancer.

Metastasis is a critical factor for the high mortality of colorectal cancer (CRC), but its mechanism is not completely understood. Epithelial-mesenchymal transition (EMT) is thought to play a key role in metastasis and also increases the cancer stem cell (CSC) feature that facilitates metastatic colonization. In this study, we investigated the biological roles of DAB2IP regulating EMT and stem cell-like features in human CRC.

Expression of HAX-1 in colorectal cancer and its role in cancer cell growth.

Colorectal cancer (CRC) is one of the most common types of cancer worldwide. Hematopoietic cell‑specific protein 1‑associated protein X‑1 (HAX‑1) has been found to be involved in several types of cancer. However, the role of HAX‑1 in CRC remains to be elucidated.

Fibroblast-Derived Exosomes Contribute to Chemoresistance through Priming Cancer Stem Cells in Colorectal Cancer.

Chemotherapy resistance observed in patients with colorectal cancer (CRC) may be related to the presence of cancer stem cells (CSCs), but the underlying mechanism(s) remain unclear. Carcinoma-associated fibroblasts (CAFs) are intimately involved in tumor recurrence, and targeting them increases chemo-sensitivity. We investigated whether fibroblasts might increase CSCs thus mediating chemotherapy resistance.

Defining the restriction point in normal asynchronous human peripheral blood lymphocytes.

Although the restriction point (R-point) was proposed in animal cells several decades ago, its existence in normal cells is still controversial, because, in most studies, long-term cultured cell lines rather than primary normal cells were used. Furthermore, cell synchronization was generally applied, resulting in growth imbalance between DNA synthesis and protein expression in cells. Finally, R-point was originally proposed as a unique arrest point that may be in G0 phase; however, generally believed R-point locates within G1 phase.

Remarkably reduced expression of FoxO3a in metaplastic colorectum, primary colorectal cancer and liver metastasis.

The forkhead family members of transcription factors (FoxOs) are expected to be potential cancer-related drug targets and thus are being extremely studied recently. In the present study, FoxO3a, one major member of this family, was identified to be down-regulated in colorectal cancer through micro-array analysis, which was confirmed by RT-PCR and Western blot in 28 patients. Moreover, immunohistochemistry (IHC) showed that the expression levels of FoxO3a were remarkably reduced in 99 cases of primary colorectal cancer, liver metastasis, and even in metaplastic colorectal tissue.

Assessment of nutritional status of clinical patients by determining normal range of oral mucosal apoptosis and proliferation rate.

The normal range of oral mucosal cell apoptosis and proliferation rate through a larger sample of non-malnourished crowd was investigated, and the nutritional status of clinical patients was assessed. Of 194 clinical patients selected according to "NRS2002" guidance, there were 167 non-malnourished patients and 27 malnourished cases, respectively. Twelve patients with toxic reactions of grade III after postoperative chemotherapy (POC) were chosen.

Expression of cyclins in high-density cultured cells and in vivo tumor cells.

It is widely assumed that during the mammalian cell cycle, four major cyclins, including G1 cyclins (D, E) and mitotic cyclins (A, B1), are expressed in an orderly scheduled pattern in exponentially cultured cells. In high-density cultured cells and in vivo growing cells, whether these cyclins are expressed in the same pattern remains unknown. In this study, we investigated the expression of cyclins by flow cytometry and western-blotting in cultured MOLT-4 and HepG2 cells at high-density.

Screening of binding proteins that interact with human Salvador 1 in a human fetal liver cDNA library by the yeast two-hybrid system.

Salvador promotes both cell cycle exit and apoptosis through the modulation of both cyclin E and Drosophila inhibitor of apoptosis protein in Drosophila. However, the cellular function of human Salvador (hSav1) is rarely reported. To screen for novel binding proteins that interact with hSav1, the cDNA of hSav1 was cloned into a bait protein plasmid, and positive clones were screened from a human fetal liver cDNA library by the yeast two-hybrid system.

Role of RANTES and its receptor in gastric cancer metastasis.

This study examined the role of regulated upon activation normal T cell expressed and secreted (RANTES) and its receptor C-C chemokine receptor type 5 (CCR5) in gastric cancer metastasis and the associated mechanism. The expression of RANTES and CCR5 was detected by using immunohistochemical staining and Western blotting in the gastric cancer tissues obtained from 60 gastric cancer patients with or without lymph node metastasis (n=30 in each). The results showed that the expression levels of RANTES and CCR5 were higher in gastric cancer with lymph node metastasis than in that without metastasis (P<0.

hSav1 interacts with HAX1 and attenuates its anti-apoptotic effects in MCF-7 breast cancer cells.

It has been reported that Salvador (SAV) is a core component of the Salvador-Warts-Hippo (SWH) pathway that restricts cell number, by functioning as a dual regulator of cell proliferation and apoptosis in Drosophila. However, the function of its human ortholog hSav1 (also called hWW45) in mammalian cells is poorly understood. In this study, we identified hematopoietic cell-specific protein 1 (HS1)-associated protein X-1 (HAX1), a 35-kDa protein localized to cell mitochondria, as a novel binding partner of hSav1 using a yeast two-hybrid screening technique.