Umetsu S, Mizukami H, Saito T, Uchida C, Igawa A, Kudo K, Itabashi C, Osonoi S, Danyang G, Sasaki T, et al. Diabetes, an independent poor prognostic factor of non-B non-C hepatocellular carcinoma, correlates with dihydropyrimidinase-like 3 promoter methylation. Sci Rep. 2020;10(1):1156.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Suh S, Kim KW. Diabetes and Cancer: Cancer should be screened in Routine Diabetes Assessment. Diabetes Metab J. 2019;43(6):733–43.

Article  PubMed  PubMed Central  Google Scholar 

Mekala MR, Bangi BB, Lebaka NJ, Nadendla RR, Ginjupally LK. Association of diabetes with oral Cancer- an enigmatic correlation. Asian Pac J Cancer Prev. 2020;21(3):809–14.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Vigneri P, Frasca F, Sciacca L, Pandini G, Vigneri R. Diabetes and cancer. Endocr Relat Cancer. 2009;16(4):1103–23.

Article  CAS  PubMed  Google Scholar 

Vacante F, Senesi P, Montesano A, Paini S, Luzi L, Terruzzi I. Metformin Counteracts HCC Progression and Metastasis Enhancing KLF6/p21 Expression and Downregulating the IGF Axis. International journal of endocrinology 2019, 2019:7570146.

Hu, Zeng Z, Xia Q, Liu Z, Feng X, Chen J, Huang M, Chen L, Fang Z, Liu Q et al. Metformin attenuates hepatoma cell proliferation by decreasing glycolytic flux through the HIF-1alpha/PFKFB3/PFK1 pathway. Life Sci 2019:116966.

Klubo-Gwiezdzinska J, Jensen K, Costello J, Patel A, Hoperia V, Bauer A, Burman KD, Wartofsky L, Vasko V. Metformin inhibits growth and decreases resistance to anoikis in medullary thyroid cancer cells. Endocr Relat Cancer. 2012;19(3):447–56.

Article  CAS  PubMed  Google Scholar 

Liu Q, Tong D, Liu G, Xu J, Do K, Geary K, Zhang D, Zhang J, Zhang Y, Li Y, et al. Metformin reverses prostate cancer resistance to enzalutamide by targeting TGF-beta1/STAT3 axis-regulated EMT. Cell Death Dis. 2017;8(8):e3007.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Russo M, Crisafulli G, Sogari A, Reilly NM, Arena S, Lamba S, Bartolini A, Amodio V, Magri A, Novara L et al. Adaptive mutability of colorectal cancers in response to targeted therapies. Science (New York, NY) 2019.

Misale S, Yaeger R, Hobor S, Scala E, Janakiraman M, Liska D, Valtorta E, Schiavo R, Buscarino M, Siravegna G, et al. Emergence of KRAS mutations and acquired resistance to anti-EGFR therapy in colorectal cancer. Nature. 2012;486(7404):532–6.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Morandi A, Indraccolo S. Linking metabolic reprogramming to therapy resistance in cancer. Biochim et Biophys acta Reviews cancer. 2017;1868(1):1–6.

Article  CAS  Google Scholar 

Hirpara J, Eu JQ, Tan JKM, Wong AL, Clement MV, Kong LR, Ohi N, Tsunoda T, Qu J, Goh BC, et al. Metabolic reprogramming of oncogene-addicted cancer cells to OXPHOS as a mechanism of drug resistance. Redox Biol. 2019;25: 101076.

Article  PubMed  Google Scholar 

Katara GK, Kulshrestha A, Mao L, Wang X, Sahoo M, Ibrahim S, Pamarthy S, Suzue K, Shekhawat GS, Gilman-Sachs A, et al. Mammary epithelium-specific inactivation of V-ATPase reduces stiffness of extracellular matrix and enhances metastasis of breast cancer. Mol Oncol. 2018;12(2):208–23.

Article  CAS  PubMed  Google Scholar 

Chakraborty S, Hong W. Linking Extracellular Matrix Agrin to the Hippo Pathway in Liver Cancer and Beyond. Cancers. 2018;10(2):45.

Article  PubMed  PubMed Central  Google Scholar 

Mouw JK, Yui Y, Damiano L, Bainer RO, Lakins JN, Acerbi I, Ou G, Wijekoon AC, Levental KR, Gilbert PM, et al. Tissue mechanics modulate microRNA-dependent PTEN expression to regulate malignant progression. Nat Med. 2014;20(4):360–7.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Morgan RL, Baack B, Smith BD, Yartel A, Pitasi M, Falck-Ytter Y. Eradication of hepatitis C virus infection and the development of hepatocellular carcinoma: a meta-analysis of observational studies. Ann Intern Med. 2013;158(5 Pt 1):329–37.

Article  PubMed  Google Scholar 

Affo S, Yu LX, Schwabe RF. The role of Cancer-Associated fibroblasts and fibrosis in Liver Cancer. Annu Rev Pathol. 2017;12:153–86.

Article  CAS  PubMed  Google Scholar 

Fattovich G, Stroffolini T, Zagni I, Donato F. Hepatocellular carcinoma in cirrhosis: incidence and risk factors. Gastroenterology. 2004;127(5 Suppl 1):35–50.

Article  Google Scholar 

Masuzaki R, Tateishi R, Yoshida H, Yoshida H, Sato S, Kato N, Kanai F, Sugioka Y, Ikeda H, Shiina S, et al. Risk assessment of hepatocellular carcinoma in chronic hepatitis C patients by transient elastography. J Clin Gastroenterol. 2008;42(7):839–43.

Article  PubMed  Google Scholar 

Masuzaki R, Tateishi R, Yoshida H, Goto E, Sato T, Ohki T, Imamura J, Goto T, Kanai F, Kato N, et al. Prospective risk assessment for hepatocellular carcinoma development in patients with chronic hepatitis C by transient elastography. Hepatology (Baltimore, MD). 2009;49(6):1954–61.

Article  PubMed  Google Scholar 

Dong Y, Xie X, Wang Z, Hu C, Zheng Q, Wang Y, Chen R, Xue T, Chen J, Gao D, et al. Increasing matrix stiffness upregulates vascular endothelial growth factor expression in hepatocellular carcinoma cells mediated by integrin beta1. Biochem Biophys Res Commun. 2014;444(3):427–32.

Article  CAS  PubMed  Google Scholar 

You Y, Zheng Q, Dong Y, Wang Y, Zhang L, Xue T, Xie X, Hu C, Wang Z, Chen R, et al. Higher Matrix Stiffness Upregulates Osteopontin expression in Hepatocellular Carcinoma cells mediated by integrin beta1/GSK3beta/beta-Catenin signaling pathway. PLoS ONE. 2015;10(8): e0134243.

Article  PubMed  PubMed Central  Google Scholar 

Zhao G, Cui J, Qin Q, Zhang J, Liu L, Deng S, Wu C, Yang M, Li S, Wang C. Mechanical stiffness of liver tissues in relation to integrin beta1 expression may influence the development of hepatic cirrhosis and hepatocellular carcinoma. J Surg Oncol. 2010;102(5):482–9.

Article  CAS  PubMed  Google Scholar 

Liu QP, Luo Q, Deng B, Ju Y, Song GB. Stiffer Matrix accelerates Migration of Hepatocellular Carcinoma cells through enhanced Aerobic Glycolysis Via the MAPK-YAP signaling. Cancers. 2020;12(2):490.

Article  CAS  PubMed  PubMed Central  Google Scholar 

You Y, Zheng Q, Dong Y, Xie X, Wang Y, Wu S, Zhang L, Wang Y, Xue T, Wang Z, et al. Matrix stiffness-mediated effects on stemness characteristics occurring in HCC cells. Oncotarget. 2016;7(22):32221–31.

Article  PubMed  PubMed Central  Google Scholar 

Dong Y, Zheng Q, Wang Z, Lin X, You Y, Wu S, Wang Y, Hu C, Xie X, Chen J, et al. Higher matrix stiffness as an independent initiator triggers epithelial-mesenchymal transition and facilitates HCC metastasis. J Hematol Oncol. 2019;12(1):112.

Article  PubMed  PubMed Central  Google Scholar 

Wu S, Zheng Q, Xing X, Dong Y, Wang Y, You Y, Chen R, Hu C, Chen J, Gao D, et al. Matrix stiffness-upregulated LOXL2 promotes fibronectin production, MMP9 and CXCL12 expression and BMDCs recruitment to assist pre-metastatic niche formation. J Experimental Clin Cancer Res CR. 2018;37(1):99.

Article  Google Scholar 

Liu C, Liu Y, Xie HG, Zhao S, Xu XX, Fan LX, Guo X, Lu T, Sun GW, Ma XJ. Role of three-dimensional matrix stiffness in regulating the chemoresistance of hepatocellular carcinoma cells. Biotechnol Appl Chem. 2015;62(4):556–62.

CAS  Google Scholar 

Schrader J, Gordon-Walker TT, Aucott RL, van Deemter M, Quaas A, Walsh S, Benten D, Forbes SJ, Wells RG, Iredale JP. Matrix stiffness modulates proliferation, chemotherapeutic response, and dormancy in hepatocellular carcinoma cells. Hepatology (Baltimore, MD). 2011;53(4):1192–205.

Article  CAS  PubMed  Google Scholar 

Gao X, Qiao X, Xing X, Huang J, Qian J, Wang Y, Zhang Y, Zhang X, Li M, Cui J, et al. Matrix stiffness-upregulated MicroRNA-17-5p attenuates the intervention Effects of Metformin on HCC Invasion and Metastasis by targeting the PTEN/PI3K/Akt pathway. Front Oncol. 2020;10: 1563.

Article  PubMed  PubMed Central  Google Scholar 

Ha Y, Fang Y, Romecin Duran PA, Tolosa EJ, Moser CD, Fernandez-Zapico ME, Roberts LR. Induction of Lysosome‐associated protein transmembrane 4 Beta via sulfatase 2 enhances autophagic flux in Liver Cancer cells. Hepatol Commun. 2019;3(11):1520–43.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Dietrich P, Hellerbrand C, Bosserhoff A. The Delta Subunit of Rod-Specific photoreceptor cGMP phosphodiesterase (PDE6D) contributes to Hepatocellular Carcinoma Progression. Cancers. 2019;11(3):398.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Richardson MM, Jennings LK, Zhang XA. Tetraspanins and tumor progression. Clin Exp Metastasis. 2011;28(3):261–70.

Article  CAS  PubMed  Google Scholar 

Chiang MY, Yangben Y, Lin NJ, Zhong JL, Yang L. Relationships among cell morphology, intrinsic cell stiffness and cell-substrate interactions. Biomaterials. 2013;34(38):9754–62.

Article  CAS  PubMed  Google Scholar 

Chou SY, Cheng CM, LeDuc PR. Composite polymer systems with control of local substrate elasticity and their effect on cytoskeletal and morphological characteristics of adherent cells. Biomaterials. 2009;30(18):3136–42.

Article  CAS  PubMed  Google Scholar 

Gopal S, Multhaupt HAB, Pocock R, Couchman JR. Cell-extracellular matrix and cell-cell adhesion are linked by syndecan-4. Matrix Biology. 2017;60–61:57–69.

Article  PubMed  Google Scholar 

Chen X, Wanggou S, Bodalia A, Zhu M, Dong W, Fan JJ, Yin WC, Min HK, Hu M, Draghici D, et al. A feedforward mechanism mediated by Mechanosensitive Ion Channel PIEZO1 and tissue mechanics promotes Glioma Aggression. Neuron. 2018;100(4):799-815e797.

Article  CAS  PubMed