Glucose starvation induces mutation and lineage-dependent adaptive responses in a large collection of cancer cell lines

Tolerance of glucose deprivation is an important factor for cancer proliferation, survival, migration and progression. To systematically understand adaptive responses under glucose starvation in cancers, we analyzed reverse phase protein array (RPPA) data of 115 protein antibodies across a panel of approximately 170 heterogeneous cancer cell lines, cultured under normal and low glucose conditions. In general, glucose starvation broadly altered levels of many of the proteins and phosphoproteins assessed across the cell lines. Many mTOR pathway components were selectively sensitive to glucose stress, although the change in their levels still varied greatly across the cell line set. Furthermore, lineage-and genotype-based classification of cancer cell lines revealed mutation-specific variation of protein expression and phosphorylation in response to glucose starvation. Decreased AKT phosphorylation (S473) was significantly associated with PTEN mutation under glucose starvation conditions in lung cancer cell lines. The present study (see TCPAportal.org for data resource) provides insight into adaptive responses to glucose deprivation under diverse cellular contexts.