Advancements in investigating Gas6<b>/</b>Axl in gastrointestinal malignant tumors_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

QIU Zhendong ^1,2 , DENG Wenhong ¹ ,  WANG Weixing ^1,2

1. Department of General Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, P. R. China;
2. Key Laboratory of Hubei Province for Digestive System Disease, Wuhan 430060, P. R. China;

Corresponding author：

WANG Weixing, Email: sate.llite@163.com

Keywords：

receptor tyrosine kinase; growth arrest specific protein 6; Axl receptor tyrosine kinase; gastrointestinal malignant tumor

DOI：

10.7507/1007-9424.202303048

Video：

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Abstract Full text Figures/Tables Video References Cited by

Objective To understand the research progress and future prospects of the growth arrest specific protein 6/Axl receptor tyrosine kinase (Gas6/Axl) signaling pathway in gastrointestinal malignant tumors. Method Retrieve relevant literature on the Gas6/Axl signaling pathway in gastrointestinal malignant tumors and analyze and summarize. Results The Gas6/Axl signaling pathway was abnormally upregulated and activated in gastrointestinal malignancies, leading to malignant cell proliferation, invasion, and metastasis, thereby promoting the occurrence and development of gastrointestinal malignancies. At present, in the field of gastrointestinal cancer, the research of Gas6/Axl signaling pathway mainly involved tumor angiogenesis, tumor drug resistance, mesenchymal epithelial transformation, and tumor microenvironment. Conclusions The Gas6/Axl signaling pathway plays a critical role in governing various cellular processes and downstream effects. Its aberrant expression contributes to the development and advancement of gastrointestinal malignancies through diverse mechanisms. Thoroughly exploring the involvement of the Gas6/Axl signaling pathway in gastrointestinal tumors is of utmost significance, as it holds the potential to unveil novel therapeutic targets for effective management of gastrointestinal malignancies.

Citation： QIU Zhendong, DENG Wenhong, WANG Weixing. Advancements in investigating Gas6/Axl in gastrointestinal malignant tumors. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2023, 30(7): 857-862. doi: 10.7507/1007-9424.202303048 Copy

1.	Alsina M, Arrazubi V, Diez M, et al. Current developments in gastric cancer: from molecular profiling to treatment strategy. Nat Rev Gastroenterol Hepatol, 2023, 20(3): 155-170.
2.	Zhan Z, Ji Y, Su H, et al. Discovery of 10 H-benzo[b] pyrido[2, 3- e][1, 4] oxazine AXL inhibitors via structure-based drug design targeting c-Met kinase. J Med Chem, 2023, 66(1): 220-234.
3.	Storey CM, Altai M, Bicak M, et al. Quantitative in vivo imaging of the androgen receptor axis reveals degree of prostate cancer radiotherapy response. Mol Cancer Res, 2023, 21(4): 307-315.
4.	Yoshimura A, Yamada T, Serizawa M, et al. High levels of AXL expression in untreated EGFR-mutated non-small cell lung cancer negatively impacts the use of osimertinib. Cancer Sci, 2023, 114(2): 606-618.
5.	van Aalen EA, Wouters SFA, Verzijl D, et al. Bioluminescent RAPPID sensors for the single-step detection of soluble Axl and multiplex analysis of cell surface cancer biomarkers. Anal Chem, 2022, 94(17): 6548-6556.
6.	Martínez-Bosch N, Cristóbal H, Iglesias M, et al. Soluble AXL is a novel blood marker for early detection of pancreatic ductal adenocarcinoma and differential diagnosis from chronic pancreatitis. EBioMedicine, 2022, 75: 103797. doi: 10.1016/j.ebiom.2021.103797.
7.	Tsukamoto S, Sugi NH, Nishibata K, et al. ER-851, a novel selective inhibitor of AXL, overcomes resistance to antimitotic drugs. Mol Cancer Ther, 2023, 22(1): 12-24.
8.	Bae D, Chaudhary P, Been JH, et al. Antitumor effect of 3-(quinolin-2-ylmethylene)-4, 6-dimethyl-5-hydroxy-7-azaoxindole down-regulating the Gas6-Axl axis. Eur J Med Chem, 2023, 251: 115274. doi: 10.1016/j.ejmech.2023.115274.
9.	Liu E, Hjelle B, Bishop JM. Transforming genes in chronic myelogenous leukemia. Proc Natl Acad Sci U S A, 1988, 85(6): 1952-1956.
10.	Goyette MA, Côté JF. AXL receptor tyrosine kinase as a promising therapeutic target directing multiple aspects of cancer progression and metastasis. Cancers (Basel), 2022, 14(3): 466. doi: 10.3390/cancers14030466.
11.	Stitt TN, Conn G, Gore M, et al. The anticoagulation factor protein S and its relative, Gas6, are ligands for the Tyro 3/Axl family of receptor tyrosine kinases. Cell, 1995, 80(4): 661-670.
12.	Mullen MM, Lomonosova E, Toboni MD, et al. GAS6/AXL inhibition enhances ovarian cancer sensitivity to chemotherapy and PARP inhibition through increased DNA damage and enhanced replication stress. Mol Cancer Res, 2022, 20(2): 265-279.
13.	Zdżalik-Bielecka D, Kozik K, Poświata A, et al. Bemcentinib and gilteritinib inhibit cell growth and impair the endo-lysosomal and autophagy systems in an AXL-independent manner. Mol Cancer Res, 2022, 20(3): 446-455.
14.	Malvankar C, Kumar D. AXL kinase inhibitors–A prospective model for medicinal chemistry strategies in anticancer drug discovery. Biochim Biophys Acta Rev Cancer, 2022, 1877(5): 188786. doi: 10.1016/j.bbcan.2022.188786.
15.	Nasimian A, Al Ashiri L, Ahmed M, et al. A Receptor tyrosine kinase inhibitor sensitivity prediction model identifies AXL dependency in leukemia. Int J Mol Sci, 2023, 24(4): 3830. doi: 10.3390/ijms24043830.
16.	Goyette MA, Duhamel S, Aubert L, et al. The receptor tyrosine kinase AXL is required at multiple steps of the metastatic cascade during HER2-positive breast cancer progression. Cell Rep, 2018, 23(5): 1476-1490.
17.	Meyer AS, Miller MA, Gertler FB, et al. The receptor AXL diversifies EGFR signaling and limits the response to EGFR-targeted inhibitors in triple-negative breast cancer cells. Sci Signal, 2013, 6(287): ra66. doi: 10.1126/scisignal.2004155.
18.	Lei T, Xu T, Zhang N, et al. Anlotinib combined with osimertinib reverses acquired osimertinib resistance in NSCLC by targeting the c-MET/MYC/AXL axis. Pharmacol Res, 2023, 188: 106668. doi: 10.1016/j.phrs.2023.106668.
19.	Schieven SM, Traets JJH, Vliet AV, et al. The elongin BC complex negatively regulates AXL and marks a differentiated phenotype in melanoma. Mol Cancer Res, 2023, 21(5): 428-443.
20.	Dharavath B, Butle A, Pal A, et al. Role of miR-944/MMP10/AXL- axis in lymph node metastasis in tongue cancer. Commun Biol, 2023, 6(1): 57. doi: 10.1038/s42003-023-04437-6.
21.	Rizzi M, Tonello S, D’Onghia D, et al. Gas6/TAM axis involvement in modulating inflammation and fibrosis in COVID-19 patients. Int J Mol Sci, 2023, 24(2): 951. doi: 10.3390/ijms24020951.
22.	Poświata A, Kozik K, Miączyńska M, et al. Endocytic trafficking of GAS6-AXL complexes is associated with sustained AKT activation. Cell Mol Life Sci, 2022, 79(6): 316. doi: 10.1007/s00018-022-04312-3.
23.	Jung H, Lee SY, Lim S, et al. Anti-inflammatory clearance of amyloid-β by a chimeric Gas6 fusion protein. Nat Med, 2022, 28(9): 1802-1812.
24.	Yong J, Elisabeth Groeger S, Ruf S, et al. Influence of leptin and compression in GAS-6 mediated homeostasis of periodontal ligament cell. Oral Dis, 2023, 29(3): 1172-1183.
25.	Ma T, Huang R, Xu Y, et al. Plasma GAS6 predicts mortality risk in acute heart failure patients: insights from the DRAGON-HF trial. J Transl Med, 2023, 21(1): 21. doi: 10.1186/s12967-022-03859-w.
26.	Xu TP, Ma P, Wang WY, et al. KLF5 and MYC modulated LINC00346 contributes to gastric cancer progression through acting as a competing endogeous RNA and indicates poor outcome. Cell Death Differ, 2019, 26(11): 2179-2193.
27.	Zhang P, Dong Q, Zhu H, et al. Long non-coding antisense RNA GAS6-AS1 supports gastric cancer progression via increasing GAS6 expression. Gene, 2019, 696: 1-9.
28.	Xia Y, Zhang R, Wang M, et al. Development and validation of a necroptosis-related gene prognostic score to predict prognosis and efficiency of immunotherapy in gastric cancer. Front Immunol, 2022, 13: 977338. doi: 10.3389/fimmu.2022.977338.
29.	Bae CA, Ham IH, Oh HJ, et al. Inhibiting the GAS6/AXL axis suppresses tumor progression by blocking the interaction between cancer-associated fibroblasts and cancer cells in gastric carcinoma. Gastric Cancer, 2020, 23(5): 824-836.
30.	Yoshioka T, Shien K, Takeda T, et al. Acquired resistance mechanisms to afatinib in HER2-amplified gastric cancer cells. Cancer Sci, 2019, 110(8): 2549-2557.
31.	Chen T, Chen J, Zeng T, et al. WZ35 inhibits gastric cancer cell metastasis by depleting glutathione to promote cellular metabolic remodeling. Cancer Lett, 2023, 555: 216044. doi: 10.1016/j.canlet.2022.216044.
32.	Choueiri TK, McDermott DF, Merchan J, et al. Belzutifan plus cabozantinib for patients with advanced clear cell renal cell carcinoma previously treated with immunotherapy: an open-label, single-arm, phase 2 study. Lancet Oncol, 2023, 24(5): 553-562.
33.	Terry S, Dalban C, Rioux-Leclercq N, et al. Association of AXL and PD-L1 expression with clinical outcomes in patients with advanced renal cell carcinoma treated with PD-1 Blockade. Clin Cancer Res, 2021, 27(24): 6749-6760.
34.	Apolo AB, Nadal R, Tomita Y, et al. Cabozantinib in patients with platinum-refractory metastatic urothelial carcinoma: an open-label, single-centre, phase 2 trial. Lancet Oncol, 2020, 21(8): 1099-1109.
35.	Huang M, Chen M, Qi M, et al. Perivascular cell-derived extracellular vesicles stimulate colorectal cancer revascularization after withdrawal of antiangiogenic drugs. J Extracell Vesicles, 2021, 10(7): e12096. doi: 10.1002/jev2.12096.
36.	Huang M, Liu M, Huang D, et al. Tumor perivascular cell-derived extracellular vesicles promote angiogenesis via the Gas6/Axl pathway. Cancer Lett, 2022, 524: 131-143.
37.	Yokoyama Y, Lew ED, Seelige R, et al. Immuno-oncological efficacy of RXDX-106, a novel TAM (TYRO3, AXL, MER) family small-molecule kinase inhibitor. Cancer Res, 2019, 79(8): 1996-2008.
38.	Cardone C, Blauensteiner B, Moreno-Viedma V, et al. AXL is a predictor of poor survival and of resistance to anti-EGFR therapy in RAS wild-type metastatic colorectal cancer. Eur J Cancer, 2020, 138: 1-10.
39.	Solanes-Casado S, Cebrián A, Rodríguez-Remírez M, et al. Overcoming PLK1 inhibitor resistance by targeting mevalonate pathway to impair AXL-TWIST axis in colorectal cancer. Biomed Pharmacother, 2021, 144: 112347. doi: 10.1016/j.biopha.2021.112347.
40.	Kawasaki Y, Miyamoto M, Oda T, et al. The novel lncRNA CALIC upregulates AXL to promote colon cancer metastasis. EMBO Rep, 2019, 20(8): e47052. doi: 10.15252/embr.201847052.
41.	Ciardiello D, Blauensteiner B, Matrone N, et al. Dual inhibition of TGFβ and AXL as a novel therapy for human colorectal adenocarcinoma with mesenchymal phenotype. Med Oncol, 2021, 38(3): 24. doi: 10.1007/s12032-021-01464-3.
42.	Liao YY, Chuang YT, Lin HY, et al. GALNT2 promotes invasiveness of colorectal cancer cells partly through AXL. Mol Oncol, 2023, 17(1): 119-133.
43.	Chen Q, Zhou L, Ma D, et al. LncRNA GAS6-AS1 facilitates tumorigenesis and metastasis of colorectal cancer by regulating TRIM14 through miR-370-3p/miR-1296-5p and FUS. J Transl Med, 2022, 20(1): 356. doi: 10.1186/s12967-022-03550-0.
44.	Lu Y, Wang W, Liu Z, et al. Long non-coding RNA profile study identifies a metabolism-related signature for colorectal cancer. Mol Med, 2021, 27(1): 83. doi: 10.1186/s10020-021-00343-x.
45.	de Souza Oliveira PF, Faria AVS, Clerici SP, et al. Violacein negatively modulates the colorectal cancer survival and epithelial-mesenchymal transition. J Cell Biochem, 2022, 123(7): 1247-1258.
46.	Chen D, Wang R, Long M, et al. Identification of in vitro and in vivo oncolytic effect in colorectal cancer cells by Orf virus strain NA1/11. Oncol Rep, 2021, 45(2): 535-546.

1. Alsina M, Arrazubi V, Diez M, et al. Current developments in gastric cancer: from molecular profiling to treatment strategy. Nat Rev Gastroenterol Hepatol, 2023, 20(3): 155-170.
2. Zhan Z, Ji Y, Su H, et al. Discovery of 10 H-benzo[b] pyrido[2, 3- e][1, 4] oxazine AXL inhibitors via structure-based drug design targeting c-Met kinase. J Med Chem, 2023, 66(1): 220-234.
3. Storey CM, Altai M, Bicak M, et al. Quantitative in vivo imaging of the androgen receptor axis reveals degree of prostate cancer radiotherapy response. Mol Cancer Res, 2023, 21(4): 307-315.
4. Yoshimura A, Yamada T, Serizawa M, et al. High levels of AXL expression in untreated EGFR-mutated non-small cell lung cancer negatively impacts the use of osimertinib. Cancer Sci, 2023, 114(2): 606-618.
5. van Aalen EA, Wouters SFA, Verzijl D, et al. Bioluminescent RAPPID sensors for the single-step detection of soluble Axl and multiplex analysis of cell surface cancer biomarkers. Anal Chem, 2022, 94(17): 6548-6556.
6. Martínez-Bosch N, Cristóbal H, Iglesias M, et al. Soluble AXL is a novel blood marker for early detection of pancreatic ductal adenocarcinoma and differential diagnosis from chronic pancreatitis. EBioMedicine, 2022, 75: 103797. doi: 10.1016/j.ebiom.2021.103797.
7. Tsukamoto S, Sugi NH, Nishibata K, et al. ER-851, a novel selective inhibitor of AXL, overcomes resistance to antimitotic drugs. Mol Cancer Ther, 2023, 22(1): 12-24.
8. Bae D, Chaudhary P, Been JH, et al. Antitumor effect of 3-(quinolin-2-ylmethylene)-4, 6-dimethyl-5-hydroxy-7-azaoxindole down-regulating the Gas6-Axl axis. Eur J Med Chem, 2023, 251: 115274. doi: 10.1016/j.ejmech.2023.115274.
9. Liu E, Hjelle B, Bishop JM. Transforming genes in chronic myelogenous leukemia. Proc Natl Acad Sci U S A, 1988, 85(6): 1952-1956.
10. Goyette MA, Côté JF. AXL receptor tyrosine kinase as a promising therapeutic target directing multiple aspects of cancer progression and metastasis. Cancers (Basel), 2022, 14(3): 466. doi: 10.3390/cancers14030466.
11. Stitt TN, Conn G, Gore M, et al. The anticoagulation factor protein S and its relative, Gas6, are ligands for the Tyro 3/Axl family of receptor tyrosine kinases. Cell, 1995, 80(4): 661-670.
12. Mullen MM, Lomonosova E, Toboni MD, et al. GAS6/AXL inhibition enhances ovarian cancer sensitivity to chemotherapy and PARP inhibition through increased DNA damage and enhanced replication stress. Mol Cancer Res, 2022, 20(2): 265-279.
13. Zdżalik-Bielecka D, Kozik K, Poświata A, et al. Bemcentinib and gilteritinib inhibit cell growth and impair the endo-lysosomal and autophagy systems in an AXL-independent manner. Mol Cancer Res, 2022, 20(3): 446-455.
14. Malvankar C, Kumar D. AXL kinase inhibitors–A prospective model for medicinal chemistry strategies in anticancer drug discovery. Biochim Biophys Acta Rev Cancer, 2022, 1877(5): 188786. doi: 10.1016/j.bbcan.2022.188786.
15. Nasimian A, Al Ashiri L, Ahmed M, et al. A Receptor tyrosine kinase inhibitor sensitivity prediction model identifies AXL dependency in leukemia. Int J Mol Sci, 2023, 24(4): 3830. doi: 10.3390/ijms24043830.
16. Goyette MA, Duhamel S, Aubert L, et al. The receptor tyrosine kinase AXL is required at multiple steps of the metastatic cascade during HER2-positive breast cancer progression. Cell Rep, 2018, 23(5): 1476-1490.
17. Meyer AS, Miller MA, Gertler FB, et al. The receptor AXL diversifies EGFR signaling and limits the response to EGFR-targeted inhibitors in triple-negative breast cancer cells. Sci Signal, 2013, 6(287): ra66. doi: 10.1126/scisignal.2004155.
18. Lei T, Xu T, Zhang N, et al. Anlotinib combined with osimertinib reverses acquired osimertinib resistance in NSCLC by targeting the c-MET/MYC/AXL axis. Pharmacol Res, 2023, 188: 106668. doi: 10.1016/j.phrs.2023.106668.
19. Schieven SM, Traets JJH, Vliet AV, et al. The elongin BC complex negatively regulates AXL and marks a differentiated phenotype in melanoma. Mol Cancer Res, 2023, 21(5): 428-443.
20. Dharavath B, Butle A, Pal A, et al. Role of miR-944/MMP10/AXL- axis in lymph node metastasis in tongue cancer. Commun Biol, 2023, 6(1): 57. doi: 10.1038/s42003-023-04437-6.
21. Rizzi M, Tonello S, D’Onghia D, et al. Gas6/TAM axis involvement in modulating inflammation and fibrosis in COVID-19 patients. Int J Mol Sci, 2023, 24(2): 951. doi: 10.3390/ijms24020951.
22. Poświata A, Kozik K, Miączyńska M, et al. Endocytic trafficking of GAS6-AXL complexes is associated with sustained AKT activation. Cell Mol Life Sci, 2022, 79(6): 316. doi: 10.1007/s00018-022-04312-3.
23. Jung H, Lee SY, Lim S, et al. Anti-inflammatory clearance of amyloid-β by a chimeric Gas6 fusion protein. Nat Med, 2022, 28(9): 1802-1812.
24. Yong J, Elisabeth Groeger S, Ruf S, et al. Influence of leptin and compression in GAS-6 mediated homeostasis of periodontal ligament cell. Oral Dis, 2023, 29(3): 1172-1183.
25. Ma T, Huang R, Xu Y, et al. Plasma GAS6 predicts mortality risk in acute heart failure patients: insights from the DRAGON-HF trial. J Transl Med, 2023, 21(1): 21. doi: 10.1186/s12967-022-03859-w.
26. Xu TP, Ma P, Wang WY, et al. KLF5 and MYC modulated LINC00346 contributes to gastric cancer progression through acting as a competing endogeous RNA and indicates poor outcome. Cell Death Differ, 2019, 26(11): 2179-2193.
27. Zhang P, Dong Q, Zhu H, et al. Long non-coding antisense RNA GAS6-AS1 supports gastric cancer progression via increasing GAS6 expression. Gene, 2019, 696: 1-9.
28. Xia Y, Zhang R, Wang M, et al. Development and validation of a necroptosis-related gene prognostic score to predict prognosis and efficiency of immunotherapy in gastric cancer. Front Immunol, 2022, 13: 977338. doi: 10.3389/fimmu.2022.977338.
29. Bae CA, Ham IH, Oh HJ, et al. Inhibiting the GAS6/AXL axis suppresses tumor progression by blocking the interaction between cancer-associated fibroblasts and cancer cells in gastric carcinoma. Gastric Cancer, 2020, 23(5): 824-836.
30. Yoshioka T, Shien K, Takeda T, et al. Acquired resistance mechanisms to afatinib in HER2-amplified gastric cancer cells. Cancer Sci, 2019, 110(8): 2549-2557.
31. Chen T, Chen J, Zeng T, et al. WZ35 inhibits gastric cancer cell metastasis by depleting glutathione to promote cellular metabolic remodeling. Cancer Lett, 2023, 555: 216044. doi: 10.1016/j.canlet.2022.216044.
32. Choueiri TK, McDermott DF, Merchan J, et al. Belzutifan plus cabozantinib for patients with advanced clear cell renal cell carcinoma previously treated with immunotherapy: an open-label, single-arm, phase 2 study. Lancet Oncol, 2023, 24(5): 553-562.
33. Terry S, Dalban C, Rioux-Leclercq N, et al. Association of AXL and PD-L1 expression with clinical outcomes in patients with advanced renal cell carcinoma treated with PD-1 Blockade. Clin Cancer Res, 2021, 27(24): 6749-6760.
34. Apolo AB, Nadal R, Tomita Y, et al. Cabozantinib in patients with platinum-refractory metastatic urothelial carcinoma: an open-label, single-centre, phase 2 trial. Lancet Oncol, 2020, 21(8): 1099-1109.
35. Huang M, Chen M, Qi M, et al. Perivascular cell-derived extracellular vesicles stimulate colorectal cancer revascularization after withdrawal of antiangiogenic drugs. J Extracell Vesicles, 2021, 10(7): e12096. doi: 10.1002/jev2.12096.
36. Huang M, Liu M, Huang D, et al. Tumor perivascular cell-derived extracellular vesicles promote angiogenesis via the Gas6/Axl pathway. Cancer Lett, 2022, 524: 131-143.
37. Yokoyama Y, Lew ED, Seelige R, et al. Immuno-oncological efficacy of RXDX-106, a novel TAM (TYRO3, AXL, MER) family small-molecule kinase inhibitor. Cancer Res, 2019, 79(8): 1996-2008.
38. Cardone C, Blauensteiner B, Moreno-Viedma V, et al. AXL is a predictor of poor survival and of resistance to anti-EGFR therapy in RAS wild-type metastatic colorectal cancer. Eur J Cancer, 2020, 138: 1-10.
39. Solanes-Casado S, Cebrián A, Rodríguez-Remírez M, et al. Overcoming PLK1 inhibitor resistance by targeting mevalonate pathway to impair AXL-TWIST axis in colorectal cancer. Biomed Pharmacother, 2021, 144: 112347. doi: 10.1016/j.biopha.2021.112347.
40. Kawasaki Y, Miyamoto M, Oda T, et al. The novel lncRNA CALIC upregulates AXL to promote colon cancer metastasis. EMBO Rep, 2019, 20(8): e47052. doi: 10.15252/embr.201847052.
41. Ciardiello D, Blauensteiner B, Matrone N, et al. Dual inhibition of TGFβ and AXL as a novel therapy for human colorectal adenocarcinoma with mesenchymal phenotype. Med Oncol, 2021, 38(3): 24. doi: 10.1007/s12032-021-01464-3.
42. Liao YY, Chuang YT, Lin HY, et al. GALNT2 promotes invasiveness of colorectal cancer cells partly through AXL. Mol Oncol, 2023, 17(1): 119-133.
43. Chen Q, Zhou L, Ma D, et al. LncRNA GAS6-AS1 facilitates tumorigenesis and metastasis of colorectal cancer by regulating TRIM14 through miR-370-3p/miR-1296-5p and FUS. J Transl Med, 2022, 20(1): 356. doi: 10.1186/s12967-022-03550-0.
44. Lu Y, Wang W, Liu Z, et al. Long non-coding RNA profile study identifies a metabolism-related signature for colorectal cancer. Mol Med, 2021, 27(1): 83. doi: 10.1186/s10020-021-00343-x.
45. de Souza Oliveira PF, Faria AVS, Clerici SP, et al. Violacein negatively modulates the colorectal cancer survival and epithelial-mesenchymal transition. J Cell Biochem, 2022, 123(7): 1247-1258.
46. Chen D, Wang R, Long M, et al. Identification of in vitro and in vivo oncolytic effect in colorectal cancer cells by Orf virus strain NA1/11. Oncol Rep, 2021, 45(2): 535-546.

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Advancements in investigating Gas6/Axl in gastrointestinal malignant tumors

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