Endometrial cancer is the sixth most common gynecologic cancer & has been reported as a malignancy arising due to idiopathic effects of certain anti-cancer agents. Tamoxifen is a drug of choice in ER positive breast cancer patients and several studies have shown good disease free survival. But, Tamoxifen needs to be prescribed for a long period of time and has been associated with resistance & a risk for endometrial malignancy. However a direct mechanistic basis for tamoxifen induced endometrial tumorigenesis is still unclear. Previous reports have shown that in cancer cells, tamoxifen treatment induced altered sub cellular localization of the oncogenic signaling kinase PAK1; our present study shows that tamoxifen induces nuclear localization of PAK1 in endometrial carcinoma cells & was mediated through JAK2 phosphorylation of PAK1 at specific residues namely Y153, Y201 & Y285. To understand the PAK1-JAK2 interaction, we used in silico tools utilizing molecular modelling and MD simulation techniques and showed that JAK2 induced phosphorylation of PAK1 is important for its altered nuclear localization and its tumorigenic effects on cancer cells.