Even though diminished expression of AnxA6 enhances cell proliferation lack of or decreased expression with the protein has become shown to become connected using a decrease from the migration of invasive breast cancer cells and chick cranial crest cells. Meanwhile, loss of AnxA6 was associated that has a delay in terminal differentiation of murine growth plate chondrocytes resulting from decreased expression of terminal differentiation markers. This suggests that AnxA6 is actually a tumor suppressor as well as a metastasis selling element. On the other hand, offered proof won’t suggests a direct involvement of AnxA6 in these cellular functions. AnxA6 presumably modulates these cellular functions as being a scaffolding protein by influencing the localization, expression amounts andor activity of other cellular factors.
The expression of epidermal development factor receptor in basal like breast cancer is connected with bad prognosis but much more importantly, it gives you the possibility to therapeutically target the receptor working with both tyrosine kinase inhibitors or therapeutic monoclonal antibodies. Although EGFR levels are elevated in quite a few cancers, its prognostic and therapeutic describes it significance in various cancers are fairly variable. This can be presumably due to the association of patient survival together with the complete receptor other than the activated receptor amounts. It is also attainable the somewhat modest EGFR prognostic value in some cancers which include breast cancer, can be as a result of modulation of its cellular amounts and activity by amongst other cellular things scaffolding proteins such as MUC4 and AnxA6. AnxA6A is largely viewed as to become a tumor suppressor. This really is based mostly on the quantity of reviews which have amply demonstrated that over expression of the protein from the non invasive A431 epidermoid carcinoma cells as well as BT20 and MDA MB 468 breast cancer cells that both lack, or express minimal levels of AnxA6 inhibited their growth.
Alternatively, down regulation of AnxA6 in MDA MB 436 and BT 549 the two of which express higher amounts of AnxA6, led to improved anchorage independent development. The inhibition of tumor cell proliferation following the expression of AnxA6 kinase inhibitor JAK Inhibitors in AnxA6 reduced cells has become shown to get partly due to the inactivation of activated EGFR as well as termination of EGFR mediated activation in the Ras pathway. These studies revealed that the AnxA6 mediated inactivation of activated EGFR and inhibition from the Ras signaling pathway had been respectively mediated by means of the interaction of AnxA6 with activated protein kinase C and p120GAP, the Ras specific guanine nucleotide activating protein. The enhanced growth of AnxA6 deficient tumor cells however is at present believed to get driven through the higher cytosolic Ca2 induced activation of PKC isoforms that in turn activate the Ras pathway independently of EGFR activity.