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Hongli Mao,1 Jinxiu Sheng,1 Jinlin Jia,1 Chang Wang,1 Shanfeng Zhang,2 Hongle Li,3 Fucheng He1 1Department of Medical Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of China; 2The Laboratory Center for Basic Medicine, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan, People’s Republic of China; 3Department of Molecular Pathology, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of ChinaCorrespondence: Fucheng HeDepartment of Medical Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, People’s Republic of ChinaEmail hefucheng@zzu.edu.cnBackground: Solute carrier family 6 member 14 (SLC6A14) is a high-capacity amino acid transporter in mammalian cells. It has gained increasing attention for its potential involvement in the progression and metabolic reprogramming of various malignant tumors. However, the role of SLC6A14 in colorectal cancer (CRC) remains unclear.Methods: Real-time polymerase chain reaction (qRT-PCR), immunoblotting and immunohistochemistry were carried out to detect the expression level of SLC6A14 in human CRC tissues and CRC-derived cell lines. HCT-116 and Caco-2 cell lines were selected to conduct in vitro functional studies. Cell Counting Kit-8 (CCK-8), colony formation, flow cytometry, cell migration and invasion assays were performed to investigate the role of SLC6A14 in CRC cells. Besides, azoxymethane/dextran sulfate sodium salt (AOM/DSS)-induced CRC and tumor xenograft models were constructed to explore the effects of SLC6A14 blockade or overexpression during tumor progression in vivo.Results: SLC6A14 was substantially increased in human CRC samples and higher levels of SLC6A14 was correlated with advanced tumor stage, lymph node metastasis and dismal survival of CRC patients. SLC6A14 markedly promoted cell growth, inhibited cell apoptosis, and exacerbated migration and invasion of CRC cells in vitro. Mechanistically, SLC6A14 aggravated these malignant phenotypes through activating JAK2/STAT3 signaling pathway, and inhibiting JAK2/STAT3 signaling with specific inhibitors could reverse SLC6A14-mediated tumorigenic effects. Besides, two different animal studies verified the tumor-promoting effect of SLC6A14 in CRC.Conclusion: Our data illustrated the crucial function of SLC6A14 during CRC progression, suggesting SLC6A14/JAK2/STAT3 axis may serve as novel therapeutic targets for patients with CRC.Keywords: SLC6A14, colorectal cancer, CRC, proliferation, migration, STAT3

Xiaoyue Zhou,1,2,* Shin-Hye Park,1,* Hongli Mao,3 Takashi Isoshima,1 Yi Wang,2 Yoshihiro Ito1,3 1Nano Medical Engineering Laboratory, RIKEN, Wako, Saitama, Japan; 2Department of Regenerative Medicine, School of Pharmaceutical Sciences, Jilin University, Changchun, Jilin, People’s Republic of China; 3Emergent Bioengineering Materials Research Team, RIKEN Center for Emergent Matter Science, Wako, Saitama, Japan *These authors contributed equally tothis work Abstract: Phosphonated gelatin was prepared for surface modification of titanium to stimulate cell functions. The modified gelatin was synthesized by coupling with 3-aminopropylphosphonic acid using water-soluble carbodiimide and characterized by 31P nuclear magnetic resonance and gel permeation chromatography. Circular dichroism revealed no differences in the conformations of unmodified and phosphonated gelatin. However, the gelation temperature was changed by the modification. Even a high concentration of modified gelatin did not form a gel at room temperature. Time-of-flight secondary ion mass spectrometry showed direct bonding between the phosphonated gelatin and the titanium surface after binding. The binding behavior of phosphonated gelatin on the titanium surface was quantitatively analyzed by a quartz crystal microbalance. Ellipsometry showed the formation of a several nanometer layer of gelatin on the surface. Contact angle measurement indicated that the modified titanium surface was hydrophobic. Enhancement of the attachment and spreading of MC-3T3L1 osteoblastic cells was observed on the phosphonated gelatin-modified titanium. These effects on cell adhesion also led to growth enhancement. Phosphonation of gelatin was effective for preparation of a cell-stimulating titanium surface. Keywords: phosphonated gelatin, surface modification, titanium, cell adhesion