Perineural invasion is related to p38 mitogen‐activated protein kinase pathway activation and promotes tumor growth and chemoresistance in pancreatic cancer

2019 ◽  
Vol 120 (7) ◽  
pp. 11775-11783 ◽  
Author(s):  
Jiangning Gu ◽  
Wei Xu ◽  
Chenghong Peng ◽  
Youwei Zhu ◽  
Di Wang ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Protein Kinase ◽  
Tumor Growth ◽  
Perineural Invasion ◽  
Mitogen Activated Protein Kinase ◽  
Pathway Activation ◽  
Mitogen Activated Protein ◽  
Kinase Pathway

scholarly journals Mitogen-Activated Protein Kinase Pathway Activation by the CD6 Lymphocyte Surface Receptor

2006 ◽  
Vol 177 (2) ◽  
pp. 1152-1159 ◽  
Author(s):  
Anna Ibáñez ◽  
Maria-Rosa Sarrias ◽  
Montserrat Farnós ◽  
Idoia Gimferrer ◽  
Carles Serra-Pagès ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Mitogen Activated Protein Kinase ◽  
Lymphocyte Surface ◽  
Pathway Activation ◽  
Mitogen Activated Protein ◽  
Surface Receptor ◽  
Kinase Pathway

scholarly journals Isoform-Specific Ras Activation and Oncogene Dependence during MYC- and Wnt-Induced Mammary Tumorigenesis

2006 ◽  
Vol 26 (21) ◽  
pp. 8109-8121 ◽  
Author(s):  
Joanne W. Jang ◽  
Robert B. Boxer ◽  
Lewis A. Chodosh
Keyword(s):  
Protein Kinase ◽  
Tumor Growth ◽  
Mapk Pathway ◽  
Mammary Tumorigenesis ◽  
Mitogen Activated Protein Kinase ◽  
Activating Mutations ◽  
Ras Activation ◽  
Pathway Activation ◽  
Induced Tumors ◽  
Mitogen Activated Protein

ABSTRACT We have previously shown that c-MYC-induced mammary tumorigenesis in mice proceeds via a preferred secondary pathway involving spontaneous activating mutations in Kras2 (C. M. D'Cruz, E. J. Gunther, R. B. Boxer, J. L. Hartman, L. Sintasath, S. E. Moody, J. D. Cox, S. I. Ha, G. K. Belka, A. Golant, R. D. Cardiff, and L. A. Chodosh, Nat. Med. 7:235-239, 2001). In contrast, we now demonstrate that Wnt1-induced mammary tumorigenesis proceeds via a pathway that preferentially activates Hras1. In addition, we find that expression of oncogenic forms of Kras2 and Hras1 from their endogenous promoters has markedly different consequences for the progression of tumors to oncogene independence. Spontaneous activating Kras2 mutations occurring in either MYC- or Wnt1-induced tumors were strongly associated with oncogene-independent tumor growth following MYC or Wnt1 downregulation. In contrast, Hras1-mutant Wnt1-induced tumors consistently remained oncogene dependent. Additionally, Kras2-mutant tumors exhibited substantially higher levels of ras-GTP, phospho-Erk1/2, and phospho-Mek1/2 compared to Hras1-mutant tumors, suggesting the involvement of the ras/mitogen-activated protein kinase (MAPK) pathway in the acquisition of oncogene independence. Consistent with this, by use of carcinogen-induced ras mutations as well as knock-in mice harboring a latent activated Kras2 allele, we demonstrate that Kras2 activation strongly synergizes with both c-MYC and Wnt1 in mammary tumorigenesis and promotes the progression of tumors to oncogene independence. Together, our findings support a model for tumorigenesis in which c-MYC and Wnt1 select for the outgrowth of cells harboring mutations in specific ras isoforms and that these secondary mutations, in turn, determine the extent of ras/MAPK pathway activation and the potential for oncogene-independent growth.

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