Question

Do KRAS mutant cells completely bypass upstream receptor tyrosine kinases?​

Answer 1

Answer:

Explanation:

It is generally accepted that KRAS mutations shortcut the signal transductions which physiologically tranfer extracellular signals into nucleus. The mutated KRAS forms a blocking configuration at GTP-binding site, and becomes constitutively active. However, there are also some literatures reporting that KRAS mutated cells do not completely bypass upstream receptors. For example, in NSCLC EGFR knockdown inhibited cell proliferation in KRAS mutated cells-in a degree much more than it affected KRAS wild type cells. (BMC Med, 2012, 10: 28) There are several other papers indicating that KRAS mutated cells still need receptor tyrosine kinases to transduce signals. Does anyone have any idea about this contradiction? Is there any clinical evidence regarding this issue?