This novel communication of above two TMEs, via the JAK pathway with PI3K/PTEN/ mTOR/AKT/GSK3β/β-catenin axis and the Ras pathway with p38/MEK/ERK/JNK axis, further fine-tunes cellular homeostasis of tumor cells, i.e., adapting to hypoxia, enhancing survival as well as promoting migration, invasion and EMT. The gene discussed is PTEN; the disease is neoplasm.