Abstract

*Parag Juvale, Dr. Sonam Kapse and Dr. Vaibhav Sunil Ladke

ABSTRACT

Oncogenic K-Ras has been implicated in most adenocarcinomas and the tumors initiated by K-Ras are known to be more aggressive as compared to the tumors initiated by other isoforms belonging to the Ras superfamily, like N-Ras and H-Ras. In spite of the essential role played by the Ras proteins in cellular signaling, their signaling has not been fully understood; Studying Ras signaling, especially for K-Ras-induced ductal adenocarcinomas, is crucial in order to develop efficient strategies to inhibit or suppress their role in tumor initiation and progression. Of the many different molecules and pathways that K-Ras triggers, calmodulin is an important one, which also has the capacity to modulate many different signaling processes, including cell proliferation pathways like the canonical and non-canonical Wnt signaling pathway and the PI3K/Akt pathway. Here we discuss in brief, the interaction of Calmodulin with K-Ras and understand how this interaction can affect the normal cellular signaling, particularly the canonical and non-canonical Wnt signaling pathway, to lead to the initiation of ductal adenocarcinomas. Interestingly, it has been seen in clinically relevant studies that Ca2+ and calmodulin levels in ductal adenocarcinomas like pancreatic adenocarcinomas, lung adenocarcinomas and colorectal carcinomas, are relatively higher; So, the probability of a functionally important interaction between K-Ras and Calmodulin needs to be intricately investigated in reference to ductal adenocarcinomas. A detailed study in this regard would help develop strategies of blocking the K-Ras-calmodulin interaction and could be of immense therapeutic value in the treatment of this dreaded category of cancers – the ductal adenocarcinomas.