Multiple evidence shows that metformin serves as a potential agent for Colorectal Cancer (CRC) treatment, while its molecular mechanisms still require detailed investigation. Here, we revealed that metformin specifically suppressed the proliferation of CRC cells by causing G1/S arrest, and INHBA is a potential target for metformin to play an anti-proliferation effect in CRC. We verified the oncogene role of INHBA by knocking down and overexpressing INHBA in CRC cells. Silencing INHBA abrogated the cell growth, while overexpression INHBA promotes the proliferation of CRC cells. As an oncogene, INHBA was aberrant overexpression in CRC tissues and closely related to the poor prognosis of CRC patients. In mechanism, INHBA is an important ligand of TGF-β signaling and metformin blocked the activation of TGF-β signaling by targeting INHBA, and then down-regulated the activity of PI3K/Akt pathway, leading to the reduction of cyclinD1 and cell cycle arrest. Together, these findings indicate that metformin down-regulates the expression of INHBA, then attenuating TGF-β/PI3K/Akt signaling transduction, thus inhibiting the proliferation of CRC. Our study elucidated a novel molecular mechanism for the anti-proliferation effect of metformin, providing a theoretical basis for the application of metformin in CRC therapy.

Single camera-based multiple-person tracking is often hindered by difficulties such as occlusion and changes in appearance. In this paper, we address such problems by proposing a robust part-based tracking-by-detection framework. Human detection using part models has become quite popular, yet its extension in tracking has not been fully explored. Our approach learns part-based person-specific SVM classifiers which capture the articulations of the human bodies in dynamically changing appearance and background. With the part-based model, our approach is able to handle partial occlusions in both the detection and the tracking stages. In the detection stage, we select the subset of parts which maximizes the probability of detection, which significantly improves the detection performance in crowded scenes. In the tracking stage, we dynamically handle occlusions by distributing the score of the learned person classifier among its corresponding parts, which allows us to detect and predict partial occlusions, and prevent the performance of the classifiers from being degraded. Extensive experiments using the proposed method on several challenging sequences demonstrate state-of-the-art performance in multiple-people tracking.

Engrailed-2 (EN2), a member of the engrailed homeobox family, has been shown to be abnormally expressed in a variety of cancers. However, the expression and the clinical significance of EN2 in colorectal cancer (CRC) are largely unknown. Firstly, we found that EN2 acted as an oncogene in CRC. EN2 was upregulated in colorectal cancer tissues compared with adjacent normal tissues. Higher EN2 expression was significantly associated with poorer survival rate. Knockdown of EN2 markedly inhibited proliferation and migration capacities of SW480 cells in vitro, and suppressed tumorigenicity in vivo. Mechanistically, Chemokine ligand 20 (CCL20), a member of the C-C motif chemokine subfamily, was identified as a direct target gene of EN2 in CRC. CCL20 expression was positively correlated with EN2 expression in CRC tissues. Moreover, EN2 promoted the proliferation and migration of CRC cells by regulating the expression of CCL20 in vitro. These results suggest that EN2 plays a critical role in the CRC tumor progression and may serve as a potential target for CRC prevention and therapy.

The mortality rate of ovarian cancer is the highest among gynaecological cancers, primarily due to metastatic symptoms. Recent studies have shown that HOX genes are crucial in tumour progression, but the underlying mechanisms remain unclear. Here, HOXC10 expression was examined in ovarian cancer tissues. The function of HOXC10 in ovarian cancer metastasis was investigated in vitroand via intraperitoneal injection in vivo. A total of 158 ovarian cancer patients with adequate records were enrolled for analysis. HOXC10 was associated with metastasis and poor prognosis in ovarian cancer. In vitro, HOXC10 overexpression promoted ovarian cancer cell migration. Moreover, HOXC10 positively regulated Slug expression, altering the migration ability of cancer cells. Furthermore, our study showed that miR-222-3p was a suppressor of HOXC10. In vivo, a decrease in hepatic metastasis was seen in xenograft mice harbouring tumours with stable HOXC10 overexpression after miR-222-3p agomir (an overexpression reagent) injection. This study provides the first evidence that HOXC10 promotes ovarian cancer metastasis by regulating the transcription of the EMT-related gene Slug. Moreover, we found that HOXC10 is regulated by miR-222-3p. These data highlight the crucial role of HOXC10 in enhancing ovarian cancer metastasis and may provide a therapeutic target for ovarian cancer.

As an important component of the innate immune system, natural killer (NK) cells have gained increasing attention in adoptive cell therapy for their safety and efficacious tumor-killing effect. Unlike T cells which rely on the interaction between TCRs and specific peptide-MHC complexes, NK cells are more prone to be served as “off-the-shelf” cell therapy products due to their rapid recognition and killing of tumor cells without MHC restriction. In recent years, constantly emerging sources of therapeutic NK cells have provided flexible options for cancer immunotherapy. Advanced genetic engineering techniques, especially chimeric antigen receptor (CAR) modification, have yielded exciting effectiveness in enhancing NK cell specificity and cytotoxicity, improving in vivo persistence, and overcoming immunosuppressive factors derived from tumors. In this review, we highlight current advances in NK-based adoptive cell therapy, including alternative sources of NK cells for adoptive infusion, various CAR modifications that confer different targeting specificity to NK cells, multiple genetic engineering strategies to enhance NK cell function, as well as the latest clinical research on adoptive NK cell therapy.

Along with abnormalities in glucose metabolism, disturbances in the balance of lipid catabolism and synthesis have emerged as a new area of cancer metabolism that needs to be studied in depth. Disturbances in lipid metabolic homeostasis, represented by fatty acid oxidation (FAO) imbalance, leading to activation of pro-cancer signals and abnormalities in the expression and activity of related metabolically critical rate-limiting enzymes, have become an important part of metabolic remodeling in cancer. The FAO process is a metabolic pathway that facilitates the breakdown of fatty acids into CO₂ and H₂O and releases large amounts of energy in the body under aerobic conditions. More and more studies have shown that FAO provides an important energy supply for the development of cancer cells. At the same time, the CPT family, including carnitine palmitoyltransferase 1 (CPT1) and carnitine palmitoyltransferase 2 (CPT2), are key rate-limiting enzymes for FAO that exert a pivotal influence on the genesis and progression of neoplastic growth. Therefore, we look at molecular structural properties of the CPT family, the roles they play in tumorigenesis and development, the target drugs, and the possible regulatory roles of CPTs in energy metabolism reprogramming to help understand the current state of CPT family research and to search for new therapeutic strategies.